chr21-42903480-T-G

Position:

• chr21-42903480-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021075.4(NDUFV3):​c.468T>G​(p.Ser156=) 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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NDUFV3	NM_021075.4	c.468T>G	p.Ser156=	synonymous_variant	3/4	ENST00000354250.7
NDUFV3	XM_011529586.3	c.468T>G	p.Ser156=	synonymous_variant	3/5
NDUFV3	NM_001001503.2	c.170-5384T>G		intron_variant
NDUFV3	XM_017028359.2	c.170-3360T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDUFV3	ENST00000354250.7	c.468T>G	p.Ser156=	synonymous_variant	3/4	1	NM_021075.4
NDUFV3	ENST00000340344.4	c.170-5384T>G		intron_variant		1		P1
NDUFV3	ENST00000460259.1	n.991T>G		non_coding_transcript_exon_variant	5/6	2
NDUFV3	ENST00000460740.1	n.360T>G		non_coding_transcript_exon_variant	2/2	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

GnomAD3 exomes AF: 0.551 AC: 138534 AN: 251430 Hom.: 40186 AF XY: 0.557 AC XY: 75681 AN XY: 135898

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 SAS exome AF: 0.567

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

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.570

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.627

Gnomad4 NFE exome AF: 0.616

Gnomad4 OTH exome AF: 0.575

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

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.561

Alfa AF: 0.588 Hom.: 41226

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.058
DANN	Benign	0.44

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;