chr21-42903400-T-C

Variant names:

• chr21-42903400-T-C
• rs11557449
• NM_021075.4:c.388T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021075.4(NDUFV3):​c.388T>C​(p.Ser130Pro) 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. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDUFV3 NM_021075.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.856

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048710555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFV3	NM_021075.4	c.388T>C	p.Ser130Pro	missense_variant	Exon 3 of 4	ENST00000354250.7	NP_066553.3
NDUFV3	XM_011529586.3	c.388T>C	p.Ser130Pro	missense_variant	Exon 3 of 5		XP_011527888.1
NDUFV3	NM_001001503.2	c.170-5464T>C		intron_variant	Intron 2 of 2		NP_001001503.1
NDUFV3	XM_017028359.2	c.170-3440T>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.388T>C	p.Ser130Pro	missense_variant	Exon 3 of 4	1	NM_021075.4	ENSP00000346196.2
NDUFV3	ENST00000340344.4	c.170-5464T>C		intron_variant	Intron 2 of 2	1		ENSP00000342895.3
NDUFV3	ENST00000460259.1	n.911T>C		non_coding_transcript_exon_variant	Exon 5 of 6	2
NDUFV3	ENST00000460740.1	n.280T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.90
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.023
Sift	Benign	0.49	T
Sift4G	Benign	0.33	T
Polyphen		0.016	B
Vest4		0.093
MutPred		0.20		Gain of catalytic residue at S130 (P = 8e-04);
MVP		0.24
MPC		0.11
ClinPred		0.034	T
GERP RS		-5.6
gMVP		0.075

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11557449; hg19: chr21-44323510;