8-132727955-A-C

Variant names:

• chr8-132727955-A-C
• rs139378594
• NM_001382403.1:c.519T>G

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.519T>G​(p.Asp173Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 152,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: 𝑓 0.000039 (0 hom., cov: 32)
• Consequence: TMEM71 NM_001382403.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 1 publications found

Genes affected

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

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=0.1029461).

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.519T>G	p.Asp173Glu	missense	Exon 6 of 10	NP_001369332.1	Q6P5X7-1
	TMEM71	NM_001382396.1		c.516T>G	p.Asp172Glu	missense	Exon 6 of 10	NP_001369325.1
	TMEM71	NM_001382397.1		c.582T>G	p.Asp194Glu	missense	Exon 7 of 11	NP_001369326.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM71	ENST00000677595.1	MANE Select	c.519T>G	p.Asp173Glu	missense	Exon 6 of 10	ENSP00000504388.1	Q6P5X7-1
	TMEM71	ENST00000356838.7	TSL:1	c.462T>G	p.Asp154Glu	missense	Exon 6 of 10	ENSP00000349296.3	Q6P5X7-2
	TMEM71	ENST00000377901.8	TSL:1	c.488-5840T>G		intron	N/A	ENSP00000367133.4	Q6P5X7-3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251008 AF XY: 0.00000737

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74322

African (AFR) AF: 0.000121 AC: 5 AN: 41430

American (AMR) AF: 0.0000655 AC: 1 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.89
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.91	T
PhyloP100		0.43
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.14
Sift	Benign	0.12	T
Sift4G	Benign	0.084	T
Polyphen		0.021	B
Vest4		0.22
MutPred		0.28		Gain of catalytic residue at W175 (P = 0.064)
MVP		0.19
MPC		0.13
ClinPred		0.59	D
GERP RS		-4.6
PromoterAI		-0.025	Neutral
gMVP		0.031
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs139378594; hg19: chr8-133740201;