chr21-42903480-T-G

Variant names:

• chr21-42903480-T-G
• rs4148973
• NM_021075.4:c.468T>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021075.4(NDUFV3):​c.468T>G​(p.Ser156Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,613,890 control chromosomes in the GnomAD database, including 294,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28603 hom., cov: 32)
  • Exomes 𝑓: 0.60 (265832 hom.)
• Consequence: NDUFV3 NM_021075.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

Genes affected

NDUFV3 (HGNC:7719): (NADH:ubiquinone oxidoreductase subunit V3) The protein encoded by this gene is one of at least forty-one subunits that make up the NADH-ubiquinone oxidoreductase complex. This complex is part of the mitochondrial respiratory chain and serves to catalyze the rotenone-sensitive oxidation of NADH and the reduction of ubiquinone. The encoded protein is one of three proteins found in the flavoprotein fraction of the complex. The specific function of the encoded protein is unknown. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 21-42903480-T-G is Benign according to our data. Variant chr21-42903480-T-G is described in ClinVar as [Benign]. Clinvar id is 1290051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFV3	NM_021075.4	c.468T>G	p.Ser156Ser	synonymous_variant	Exon 3 of 4	ENST00000354250.7	NP_066553.3
NDUFV3	XM_011529586.3	c.468T>G	p.Ser156Ser	synonymous_variant	Exon 3 of 5		XP_011527888.1
NDUFV3	NM_001001503.2	c.170-5384T>G		intron_variant	Intron 2 of 2		NP_001001503.1
NDUFV3	XM_017028359.2	c.170-3360T>G		intron_variant	Intron 2 of 3		XP_016883848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFV3	ENST00000354250.7	c.468T>G	p.Ser156Ser	synonymous_variant	Exon 3 of 4	1	NM_021075.4	ENSP00000346196.2
NDUFV3	ENST00000340344.4	c.170-5384T>G		intron_variant	Intron 2 of 2	1		ENSP00000342895.3
NDUFV3	ENST00000460259.1	n.991T>G		non_coding_transcript_exon_variant	Exon 5 of 6	2
NDUFV3	ENST00000460740.1	n.360T>G		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91900 AN: 151918 Hom.: 28560 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.557

GnomAD2 exomes AF: 0.551 AC: 138534 AN: 251430 AF XY: 0.557

Gnomad AFR exome AF: 0.720

Gnomad AMR exome AF: 0.335

Gnomad ASJ exome AF: 0.578

Gnomad EAS exome AF: 0.329

Gnomad FIN exome AF: 0.628

Gnomad NFE exome AF: 0.608

Gnomad OTH exome AF: 0.541

GnomAD4 exome AF: 0.599 AC: 875170 AN: 1461854 Hom.: 265832 Cov.: 71 AF XY: 0.598 AC XY: 435071 AN XY: 727226

Gnomad4 AFR exome AF: 0.718 AC: 24028 AN: 33480

Gnomad4 AMR exome AF: 0.345 AC: 15424 AN: 44724

Gnomad4 ASJ exome AF: 0.570 AC: 14909 AN: 26136

Gnomad4 EAS exome AF: 0.366 AC: 14515 AN: 39700

Gnomad4 SAS exome AF: 0.573 AC: 49432 AN: 86256

Gnomad4 FIN exome AF: 0.627 AC: 33480 AN: 53406

Gnomad4 NFE exome AF: 0.616 AC: 685488 AN: 1111998

Gnomad4 Remaining exome AF: 0.575 AC: 34737 AN: 60390

GnomAD4 genome AF: 0.605 AC: 91991 AN: 152036 Hom.: 28603 Cov.: 32 AF XY: 0.602 AC XY: 44732 AN XY: 74332

Gnomad4 AFR AF: 0.713 AC: 0.712811 AN: 0.712811

Gnomad4 AMR AF: 0.428 AC: 0.428216 AN: 0.428216

Gnomad4 ASJ AF: 0.573 AC: 0.573445 AN: 0.573445

Gnomad4 EAS AF: 0.339 AC: 0.339389 AN: 0.339389

Gnomad4 SAS AF: 0.560 AC: 0.559726 AN: 0.559726

Gnomad4 FIN AF: 0.629 AC: 0.629038 AN: 0.629038

Gnomad4 NFE AF: 0.602 AC: 0.601751 AN: 0.601751

Gnomad4 OTH AF: 0.561 AC: 0.560606 AN: 0.560606

Alfa AF: 0.589 Hom.: 50830

Bravo AF: 0.591

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.058
DANN	Benign	0.44
Mutation Taster		=100/0	polymorphism (auto)

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

LitVar

Other links and lift over

dbSNP: rs4148973; hg19: chr21-44323590; COSMIC: COSV61087771;