rs2839600

Variant names:

• chr21-42897199-T-C
• rs2839600
• NM_021075.4:c.169+152T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 -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 rank	MANE	Protein	UniProt
NDUFV3	NM_021075.4	c.169+152T>C		intron_variant	Intron 2 of 3	ENST00000354250.7	NP_066553.3
NDUFV3	NM_001001503.2	c.169+152T>C		intron_variant	Intron 2 of 2		NP_001001503.1
NDUFV3	XM_011529586.3	c.169+152T>C		intron_variant	Intron 2 of 4		XP_011527888.1
NDUFV3	XM_017028359.2	c.169+152T>C		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.169+152T>C		intron_variant	Intron 2 of 3	1	NM_021075.4	ENSP00000346196.2
NDUFV3	ENST00000340344.4	c.169+152T>C		intron_variant	Intron 2 of 2	1		ENSP00000342895.3
NDUFV3	ENST00000460259.1	n.692+152T>C		intron_variant	Intron 4 of 5	2
NDUFV3	ENST00000460740.1	n.61+3818T>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.105 AC: 1928 AN: 18408

American (AMR) AF: 0.150 AC: 4724 AN: 31588

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3042 AN: 19712

East Asian (EAS) AF: 0.316 AC: 9847 AN: 31160

South Asian (SAS) AF: 0.237 AC: 14954 AN: 63174

European-Finnish (FIN) AF: 0.129 AC: 4528 AN: 35000

Middle Eastern (MID) AF: 0.124 AC: 350 AN: 2822

European-Non Finnish (NFE) AF: 0.133 AC: 66304 AN: 497678

Other (OTH) AF: 0.146 AC: 5180 AN: 35510

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

African (AFR) AF: 0.109 AC: 4538 AN: 41564

American (AMR) AF: 0.142 AC: 2174 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1481 AN: 5170

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1600 AN: 10584

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9264 AN: 68002

Other (OTH) AF: 0.151 AC: 320 AN: 2114

Alfa AF: 0.142 Hom.: 3084

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
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2839600; hg19: chr21-44317309;