rs2339844

Variant names:

• chr3-179604597-A-C
• rs2339844
• ENST00000392659.2:c.-157T>G

Your query was ambiguous. Multiple possible variants found:

• chr3-179604597-A-C
• chr3-179604597-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177988.1(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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.091 (689 hom., cov: 33)
  • Exomes 𝑓: 0.085 (6114 hom.)
• Consequence: MRPL47 NM_177988.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61
• Publications: 26 publications found

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]

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]

ENSG00000288698 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177988.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL47	NM_020409.3	MANE Select	c.28T>G	p.Cys10Gly	missense	Exon 1 of 7	NP_065142.2
	MRPL47	NM_177988.1		c.-157T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_817125.1	Q9HD33-3
	MRPL47	NM_177988.1		c.-157T>G		5_prime_UTR	Exon 1 of 6	NP_817125.1	Q9HD33-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRPL47	ENST00000392659.2	TSL:1	c.-157T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000376427.2	Q9HD33-3
	MRPL47	ENST00000476781.6	TSL:1 MANE Select	c.28T>G	p.Cys10Gly	missense	Exon 1 of 7	ENSP00000417602.1	Q9HD33-1
	MRPL47	ENST00000259038.6	TSL:1	c.28T>G	p.Cys10Gly	missense	Exon 1 of 7	ENSP00000259038.2	Q9HD33-2

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13842 AN: 152168 Hom.: 686 Cov.: 33

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

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.: 32 AF XY: 0.0875 AC XY: 63651 AN XY: 727204

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

GnomAD4 genome AF: 0.0911 AC: 13867 AN: 152286 Hom.: 689 Cov.: 33 AF XY: 0.0942 AC XY: 7012 AN XY: 74458

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: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0760 AC: 5166 AN: 68018

Other (OTH) AF: 0.0880 AC: 186 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.65
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.6
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.066
Sift	Benign	0.26	T
Sift4G	Benign	0.27	T
Polyphen		0.0020	B
Vest4		0.50
MPC		0.17
ClinPred		0.035	T
GERP RS		5.1
PromoterAI		0.0080	Neutral
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)

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

Other links and lift over

dbSNP: rs2339844; hg19: chr3-179322385; COSMIC: COSV52019701; COSMIC: COSV52019701;