dbSNP rs34804805: MRPL35:p.Phe6Val (chr2-86199506-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016622.4(MRPL35):c.16T>G(p.Phe6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

MRPL35
NM_016622.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0290

Publications

4 publications found

Variant links:

Genes affected

MRPL35 (HGNC:14489): (mitochondrial ribosomal protein L35) 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. Sequence analysis identified three transcript variants. Pseudogenes corresponding to this gene are found on chromosomes 6p, 10q, and Xp. [provided by RefSeq, Jul 2008]

MRPL35 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053610206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRPL35	NM_016622.4 link	c.16T>G	p.Phe6Val	missense_variant	Exon 1 of 4	ENST00000337109.9	NP_057706.2	Q9NZE8-1
MRPL35	NM_001363782.1 link	c.16T>G	p.Phe6Val	missense_variant	Exon 1 of 5		NP_001350711.1
MRPL35	NM_145644.3 link	c.16T>G	p.Phe6Val	missense_variant	Exon 1 of 5		NP_663619.1	Q9NZE8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MRPL35	ENST00000337109.9 link	c.16T>G	p.Phe6Val	missense_variant	Exon 1 of 4	1	NM_016622.4	ENSP00000338389.4	Q9NZE8-1
MRPL35	ENST00000254644.12 link	c.16T>G	p.Phe6Val	missense_variant	Exon 1 of 5	1		ENSP00000254644.7	Q9NZE8-2
MRPL35	ENST00000409180.1 link	c.16T>G	p.Phe6Val	missense_variant	Exon 1 of 5	3		ENSP00000386255.1	D3YTC1
MRPL35	ENST00000605125.5 link	c.16T>G	p.Phe6Val	missense_variant	Exon 1 of 3	2		ENSP00000473925.1	S4R348

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000549

AC:

138

AN:

251366

AF XY:

0.000471

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000209

AC:

305

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

150

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00286

AC:

128

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000138

AC:

154

AN:

1112008

Other (OTH)

AF:

0.000381

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000460

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41576

American (AMR)

AF:

0.00320

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68036

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000439

Hom.:

Bravo

AF:

0.000586

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.4

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0069

.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.59

T;T;T;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.0054

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.0

M;.;M;.

PhyloP100

0.029

PrimateAI

Benign

0.45

PROVEAN

Benign

0.18

N;.;N;N

REVEL

Benign

0.018

Sift

Uncertain

0.011

D;.;D;D

Sift4G

Benign

0.64

T;D;T;T

Polyphen

0.0040

.;.;B;.

Vest4

0.33

MVP

0.030

MPC

0.18

ClinPred

0.060

GERP RS

-1.2

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.38

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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