21-42881346-A-G

Variant names:

• chr21-42881346-A-G
• rs2839597
• XM_024452048.2:c.-349-4579T>C

Variant summary

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

The ENST00000460259.1(NDUFV3):​n.222+1481A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,214 control chromosomes in the GnomAD database, including 1,304 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 0.13 (1304 hom., cov: 32)
• Consequence: NDUFV3 ENST00000460259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• Publications: 5 publications found

Genes affected

WDR4 (HGNC:12756): (WD repeat domain 4) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is excluded as a candidate for a form of nonsyndromic deafness (DFNB10), but is still a candidate for other disorders mapped to 21q22.3 as well as for the development of Down syndrome phenotypes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]

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]

LOC105372817 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000460259.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFV3	ENST00000460259.1	TSL:2	n.222+1481A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19769 AN: 152096 Hom.: 1301 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.137

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19791 AN: 152214 Hom.: 1304 Cov.: 32 AF XY: 0.135 AC XY: 10021 AN XY: 74418

African (AFR) AF: 0.107 AC: 4429 AN: 41536

American (AMR) AF: 0.125 AC: 1910 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3468

East Asian (EAS) AF: 0.234 AC: 1209 AN: 5170

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4828

European-Finnish (FIN) AF: 0.147 AC: 1562 AN: 10592

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8693 AN: 68018

Other (OTH) AF: 0.141 AC: 298 AN: 2114

Alfa AF: 0.117 Hom.: 673

Bravo AF: 0.127

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.51
PhyloP100		-0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2839597; hg19: chr21-44301456;