Variant 5-73131606-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173490.8(TMEM171):c.851C>T(p.Thr284Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TMEM171
NM_173490.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.133

Variant links:

Genes affected

TMEM171 (HGNC:27031): (transmembrane protein 171) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM171 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.09533569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM171	NM_173490.8 linkuse as main transcript	c.851C>T	p.Thr284Met	missense_variant	4/4	ENST00000454765.7	NP_775761.4	Q8WVE6-1
TMEM171	NM_001161342.3 linkuse as main transcript	c.848C>T	p.Thr283Met	missense_variant	4/4		NP_001154814.1	Q8WVE6-2
TMEM171	XM_011543156.2 linkuse as main transcript	c.794C>T	p.Thr265Met	missense_variant	4/4		XP_011541458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM171	ENST00000454765.7 linkuse as main transcript	c.851C>T	p.Thr284Met	missense_variant	4/4	1	NM_173490.8	ENSP00000415030.2		Q8WVE6-1
TMEM171	ENST00000287773.5 linkuse as main transcript	c.848C>T	p.Thr283Met	missense_variant	4/4	5		ENSP00000287773.5		Q8WVE6-2

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251098

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461664

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000856

AC:

AN:

151934

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000960

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 08, 2024

The c.851C>T (p.T284M) alteration is located in exon 4 (coding exon 3) of the TMEM171 gene. This alteration results from a C to T substitution at nucleotide position 851, causing the threonine (T) at amino acid position 284 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.2

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.095

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.084

Sift

Benign

0.098

T;T

Sift4G

Uncertain

0.057

T;T

Polyphen

0.98

D;D

Vest4

0.11

MVP

0.21

MPC

0.090

ClinPred

0.091

GERP RS

3.3

Varity_R

0.024

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over