NM_021075.4:c.334G>C

Variant names:

• chr21-42903346-G-C
• rs372515876
• NM_021075.4:c.334G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021075.4(NDUFV3):​c.334G>C​(p.Val112Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V112I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDUFV3 NM_021075.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.721
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027400523).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021075.4. 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
	NDUFV3	NM_021075.4	MANE Select	c.334G>C	p.Val112Leu	missense	Exon 3 of 4	NP_066553.3
	NDUFV3	NM_001001503.2		c.170-5518G>C		intron	N/A	NP_001001503.1	P56181-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFV3	ENST00000354250.7	TSL:1 MANE Select	c.334G>C	p.Val112Leu	missense	Exon 3 of 4	ENSP00000346196.2	P56181-2
	NDUFV3	ENST00000340344.4	TSL:1	c.170-5518G>C		intron	N/A	ENSP00000342895.3	P56181-1
	NDUFV3	ENST00000942160.1		c.328G>C	p.Val110Leu	missense	Exon 3 of 4	ENSP00000612219.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.082
DANN	Benign	0.29
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.72
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.028
Sift	Benign	1.0	T
Sift4G	Benign	0.82	T
Polyphen		0.0020	B
Vest4		0.041
MutPred		0.080		Loss of sheet (P = 0.0817)
MVP		0.35
MPC		0.083
ClinPred		0.023	T
GERP RS		-3.4
gMVP		0.039
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs372515876; hg19: chr21-44323456;