Variant 5-73123503-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000454765.7(TMEM171):c.130T>C(p.Phe44Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000849 in 1,614,208 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

TMEM171
ENST00000454765.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024934083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM171	NM_173490.8 linkuse as main transcript	c.130T>C	p.Phe44Leu	missense_variant	2/4	ENST00000454765.7	NP_775761.4
TMEM171	NM_001161342.3 linkuse as main transcript	c.130T>C	p.Phe44Leu	missense_variant	2/4		NP_001154814.1
TMEM171	XM_011543156.2 linkuse as main transcript	c.130T>C	p.Phe44Leu	missense_variant	2/4		XP_011541458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM171	ENST00000454765.7 linkuse as main transcript	c.130T>C	p.Phe44Leu	missense_variant	2/4	1	NM_173490.8	ENSP00000415030	P4	Q8WVE6-1
TMEM171	ENST00000287773.5 linkuse as main transcript	c.130T>C	p.Phe44Leu	missense_variant	2/4	5		ENSP00000287773	A2	Q8WVE6-2

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.000103

AC:

AN:

251456

Hom.:

AF XY:

0.0000662

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000440

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000451

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

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

Aug 12, 2022

The c.130T>C (p.F44L) alteration is located in exon 2 (coding exon 1) of the TMEM171 gene. This alteration results from a T to C substitution at nucleotide position 130, causing the phenylalanine (F) at amino acid position 44 to be replaced by a leucine (L). 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

Pathogenic

0.91

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.012

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.61

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.76

N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.071

Sift

Benign

0.22

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.035

B;B

Vest4

0.14

MutPred

0.31

Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);

MVP

0.30

MPC

0.27

ClinPred

0.079

GERP RS

5.1

Varity_R

0.26

gMVP

0.30

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