3-179604597-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000392659.2(MRPL47):c.-157T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,614,094 control chromosomes in the GnomAD database, including 6,803 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.091 ( 689 hom., cov: 33)

Exomes 𝑓: 0.085 ( 6114 hom. )

Consequence

MRPL47
ENST00000392659.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.61

Publications

26 publications found

Variant links:

Genes affected

MRPL47 (HGNC:16652): (mitochondrial ribosomal protein L47) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein. This gene is immediately adjacent to the gene for BAF complex 53 kDa subunit protein a (BAF53a), in a tail-to-tail orientation. Two transcript variants encoding different protein isoforms have been identified. [provided by RefSeq, Jul 2008]

MRPL47 links:

NDUFB5 (HGNC:7700): (NADH:ubiquinone oxidoreductase subunit B5) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

NDUFB5 links:

ENSG00000288698 (HGNC:):

ENSG00000288698 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014838278).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL47	NM_020409.3 link	c.28T>G	p.Cys10Gly	missense_variant	Exon 1 of 7	ENST00000476781.6	NP_065142.2	Q9HD33-1
NDUFB5	NM_002492.4 link	c.-219A>C		upstream_gene_variant		ENST00000259037.8	NP_002483.1	O43674-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRPL47	ENST00000476781.6 link	c.28T>G	p.Cys10Gly	missense_variant	Exon 1 of 7	1	NM_020409.3	ENSP00000417602.1	Q9HD33-1
NDUFB5	ENST00000259037.8 link	c.-219A>C		upstream_gene_variant		1	NM_002492.4	ENSP00000259037.3	O43674-1
ENSG00000288698	ENST00000680408.1 link	n.-219A>C		upstream_gene_variant				ENSP00000506198.1	A0A7P0TAR2

Frequencies

GnomAD3 genomes

AF:

0.0910

AC:

13842

AN:

152168

Hom.:

686

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0956

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0640

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.0809

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0759

Gnomad OTH

AF:

0.0894

GnomAD2 exomes

AF:

0.104

AC:

26214

AN:

251370

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.0951

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0646

Gnomad EAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0839

Gnomad NFE exome

AF:

0.0757

Gnomad OTH exome

AF:

0.0951

GnomAD4 exome

AF:

0.0854

AC:

124869

AN:

1461808

Hom.:

6114

Cov.:

AF XY:

0.0875

AC XY:

63651

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0983

AC:

3292

AN:

33476

American (AMR)

AF:

0.164

AC:

7350

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0645

AC:

1686

AN:

26134

East Asian (EAS)

AF:

0.126

AC:

4982

AN:

39694

South Asian (SAS)

AF:

0.170

AC:

14652

AN:

86252

European-Finnish (FIN)

AF:

0.0824

AC:

4402

AN:

53414

Middle Eastern (MID)

AF:

0.0491

AC:

283

AN:

5768

European-Non Finnish (NFE)

AF:

0.0748

AC:

83124

AN:

1111960

Other (OTH)

AF:

0.0844

AC:

5098

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

6265

12529

18794

25058

31323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3206

6412

9618

12824

16030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0911

AC:

13867

AN:

152286

Hom.:

689

Cov.:

AF XY:

0.0942

AC XY:

7012

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0960

AC:

3988

AN:

41558

American (AMR)

AF:

0.124

AC:

1893

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0640

AC:

222

AN:

3468

East Asian (EAS)

AF:

0.112

AC:

579

AN:

5182

South Asian (SAS)

AF:

0.174

AC:

839

AN:

4824

European-Finnish (FIN)

AF:

0.0809

AC:

859

AN:

10618

Middle Eastern (MID)

AF:

0.0788

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0760

AC:

5166

AN:

68018

Other (OTH)

AF:

0.0880

AC:

186

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

649

1299

1948

2598

3247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0818

Hom.:

2827

Bravo

AF:

0.0920

TwinsUK

AF:

0.0723

AC:

268

ALSPAC

AF:

0.0695

AC:

268

ESP6500AA

AF:

0.0924

AC:

407

ESP6500EA

AF:

0.0785

AC:

675

ExAC

AF:

0.102

AC:

12341

Asia WGS

AF:

0.118

AC:

411

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0072

T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M

PhyloP100

2.6

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.066

Sift

Benign

0.26

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0020

B;B

Vest4

0.50

MPC

0.17

ClinPred

0.035

GERP RS

5.1

PromoterAI

0.0080

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

gMVP

0.62

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over