rs2839600

Positions:

• chr21-42897199-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021075.4(NDUFV3):​c.169+152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 887,262 control chromosomes in the GnomAD database, including 11,208 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 0.14 (1520 hom., cov: 32)
  • Exomes 𝑓: 0.15 (9688 hom.)
• Consequence: NDUFV3 NM_021075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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]

NDUFV3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFV3	NM_021075.4	c.169+152T>C		intron_variant		ENST00000354250.7	NP_066553.3
NDUFV3	NM_001001503.2	c.169+152T>C		intron_variant			NP_001001503.1
NDUFV3	XM_011529586.3	c.169+152T>C		intron_variant			XP_011527888.1
NDUFV3	XM_017028359.2	c.169+152T>C		intron_variant			XP_016883848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFV3	ENST00000354250.7	c.169+152T>C		intron_variant		1	NM_021075.4	ENSP00000346196.2
NDUFV3	ENST00000340344.4	c.169+152T>C		intron_variant		1		ENSP00000342895.3
NDUFV3	ENST00000460259.1	n.692+152T>C		intron_variant		2
NDUFV3	ENST00000460740.1	n.61+3818T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21187 AN: 152092 Hom.: 1517 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.151 AC: 110857 AN: 735052 Hom.: 9688 AF XY: 0.155 AC XY: 59321 AN XY: 382590

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.237

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.139 AC: 21205 AN: 152210 Hom.: 1520 Cov.: 32 AF XY: 0.145 AC XY: 10759 AN XY: 74408

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.151

Alfa AF: 0.143 Hom.: 2255

Bravo AF: 0.138

Asia WGS AF: 0.260 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2839600; hg19: chr21-44317309;