8-132714174-G-C

Variant names:

• chr8-132714174-G-C
• rs2131000484
• NM_001382403.1:c.794C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001382403.1(TMEM71):​c.794C>G​(p.Ser265*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM71 NM_001382403.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 0 publications found

Genes affected

TMEM71 (HGNC:26572): (transmembrane protein 71) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000287095 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382403.1. 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
	TMEM71	NM_001382403.1	MANE Select	c.794C>G	p.Ser265*	stop_gained	Exon 8 of 10	NP_001369332.1	Q6P5X7-1
	TMEM71	NM_001382396.1		c.791C>G	p.Ser264*	stop_gained	Exon 8 of 10	NP_001369325.1
	TMEM71	NM_001382397.1		c.857C>G	p.Ser286*	stop_gained	Exon 9 of 11	NP_001369326.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM71	ENST00000677595.1	MANE Select	c.794C>G	p.Ser265*	stop_gained	Exon 8 of 10	ENSP00000504388.1	Q6P5X7-1
	TMEM71	ENST00000356838.7	TSL:1	c.737C>G	p.Ser246*	stop_gained	Exon 8 of 10	ENSP00000349296.3	Q6P5X7-2
	TMEM71	ENST00000377901.8	TSL:1	c.605C>G	p.Ser202*	stop_gained	Exon 7 of 9	ENSP00000367133.4	Q6P5X7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	34
DANN	Benign	0.94
Eigen	Benign	0.17
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.14	N
PhyloP100		2.1
Vest4		0.10
GERP RS		3.8
Mutation Taster		=77/123	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs2131000484; hg19: chr8-133726420; COSMIC: COSV63458662;