19-8311566-G-T

Variant names:

• chr19-8311566-G-T
• NM_005001.5:c.281C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005001.5(NDUFA7):​c.281C>A​(p.Ala94Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NDUFA7 NM_005001.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.31

Genes affected

NDUFA7 (HGNC:7691): (NADH:ubiquinone oxidoreductase subunit A7) This gene encodes a subunit of NADH:ubiquinone oxidoreductase (complex I), which is a multiprotein complex located in the inner mitochondrial membrane. Complex I functions in the transfer of electrons from NADH to the respiratory chain. [provided by RefSeq, Mar 2011]

ENSG00000167774 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23156351).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDUFA7	NM_005001.5	c.281C>A	p.Ala94Glu	missense_variant	Exon 4 of 4	ENST00000301457.3	NP_004992.2
NDUFA7	NR_135539.2	n.298C>A		non_coding_transcript_exon_variant	Exon 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDUFA7	ENST00000301457.3	c.281C>A	p.Ala94Glu	missense_variant	Exon 4 of 4	1	NM_005001.5	ENSP00000301457.1
ENSG00000167774	ENST00000598884.1	n.281C>A		non_coding_transcript_exon_variant	Exon 4 of 5	4		ENSP00000470609.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460246 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726368

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Benign	0.0013
Eigen_PC	Benign	-0.026
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.080	T
Sift4G	Benign	0.30	T
Polyphen		0.84	P
Vest4		0.28
MutPred		0.34		Gain of sheet (P = 0.0266);
MVP		0.40
MPC		0.40
ClinPred		0.95	D
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-8376450;