19-14566252-T-A

Variant names:

• chr19-14566252-T-A
• rs768959190
• NM_004146.6:c.295A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004146.6(NDUFB7):​c.295A>T​(p.Met99Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: NDUFB7 NM_004146.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

Genes affected

NDUFB7 (HGNC:7702): (NADH:ubiquinone oxidoreductase subunit B7) The protein encoded by this gene is a subunit of the multisubunit NADH:ubiquinone oxidoreductase (complex I). Mammalian complex I is composed of 45 different subunits. It is located at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38310063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFB7	NM_004146.6	c.295A>T	p.Met99Leu	missense_variant	Exon 3 of 3	ENST00000215565.3	NP_004137.2
NDUFB7	XM_011528039.4	c.181A>T	p.Met61Leu	missense_variant	Exon 3 of 3		XP_011526341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFB7	ENST00000215565.3	c.295A>T	p.Met99Leu	missense_variant	Exon 3 of 3	1	NM_004146.6	ENSP00000215565.1
NDUFB7	ENST00000593353.5	n.*80A>T		non_coding_transcript_exon_variant	Exon 3 of 3	2		ENSP00000473120.1
NDUFB7	ENST00000593353.5	n.*80A>T		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000473120.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250316 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135660

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	2.9	M
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.17
Sift	Benign	0.084	T
Sift4G	Benign	0.085	T
Polyphen		0.73	P
Vest4		0.35
MutPred		0.59		Gain of methylation at K100 (P = 0.0377);
MVP		0.41
MPC		0.14
ClinPred		0.80	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs768959190; hg19: chr19-14677064;