8-73976433-G-C

Variant names:

• chr8-73976433-G-C
• NM_017866.6:c.152G>C

Variant summary

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

The NM_017866.6(TMEM70):​c.152G>C​(p.Gly51Ala) 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. 13/21 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: 33)
• Consequence: TMEM70 NM_017866.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939

Genes affected

TMEM70 (HGNC:26050): (transmembrane protein 70) This gene likely encodes a mitochondrial membrane protein. The encoded protein may play a role in biogenesis of mitochondrial ATP synthase. Mutations in this gene have been associated with neonatal mitochondrial encephalocardiomyopathy due to ATP synthase deficiency. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

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=0.085356355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM70	NM_017866.6	c.152G>C	p.Gly51Ala	missense_variant	Exon 1 of 3	ENST00000312184.6	NP_060336.3
TMEM70	NM_001040613.3	c.152G>C	p.Gly51Ala	missense_variant	Exon 1 of 3		NP_001035703.1
TMEM70	NR_033334.2	n.239G>C		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM70	ENST00000312184.6	c.152G>C	p.Gly51Ala	missense_variant	Exon 1 of 3	1	NM_017866.6	ENSP00000312599.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.3
DANN	Benign	0.63
DEOGEN2	Benign	0.0046	.;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D;N
REVEL	Benign	0.070
Sift	Benign	0.37	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.24	.;B
Vest4		0.054
MutPred		0.29		Gain of sheet (P = 0.0085);Gain of sheet (P = 0.0085);
MVP		0.13
MPC		0.25
ClinPred		0.33	T
GERP RS		3.1
Varity_R		0.036
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-74888668;