rs2131000484

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-132714174-G-A
• chr8-132714174-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001382403.1(TMEM71):​c.794C>T​(p.Ser265Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMEM71 NM_001382403.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19653285).

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>T	p.Ser265Leu	missense	Exon 8 of 10	NP_001369332.1	Q6P5X7-1
	TMEM71	NM_001382396.1		c.791C>T	p.Ser264Leu	missense	Exon 8 of 10	NP_001369325.1
	TMEM71	NM_001382397.1		c.857C>T	p.Ser286Leu	missense	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>T	p.Ser265Leu	missense	Exon 8 of 10	ENSP00000504388.1	Q6P5X7-1
	TMEM71	ENST00000356838.7	TSL:1	c.737C>T	p.Ser246Leu	missense	Exon 8 of 10	ENSP00000349296.3	Q6P5X7-2
	TMEM71	ENST00000377901.8	TSL:1	c.605C>T	p.Ser202Leu	missense	Exon 7 of 9	ENSP00000367133.4	Q6P5X7-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460546 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726636

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5156

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111512

Other (OTH) AF: 0.00 AC: 0 AN: 60300

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.2
DANN	Uncertain	0.99
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.10
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.19	T
Polyphen		0.87	P
Vest4		0.24
MutPred		0.56		Gain of stability (P = 0.1689)
MVP		0.19
MPC		0.044
ClinPred		0.23	T
GERP RS		3.8
gMVP		0.35
Mutation Taster		=92/8	polymorphism

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;