Variant 5-73123552-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_173490.8(TMEM171):c.179A>G(p.Lys60Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000576 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

TMEM171
NM_173490.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3984871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM171	NM_173490.8 linkuse as main transcript	c.179A>G	p.Lys60Arg	missense_variant	2/4	ENST00000454765.7	NP_775761.4	Q8WVE6-1
TMEM171	NM_001161342.3 linkuse as main transcript	c.179A>G	p.Lys60Arg	missense_variant	2/4		NP_001154814.1	Q8WVE6-2
TMEM171	XM_011543156.2 linkuse as main transcript	c.179A>G	p.Lys60Arg	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.179A>G	p.Lys60Arg	missense_variant	2/4	1	NM_173490.8	ENSP00000415030.2		Q8WVE6-1
TMEM171	ENST00000287773.5 linkuse as main transcript	c.179A>G	p.Lys60Arg	missense_variant	2/4	5		ENSP00000287773.5		Q8WVE6-2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

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:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251358

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000145

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:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000499

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000134

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:

0.0000324

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000131

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000751

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

Oct 20, 2024

The c.179A>G (p.K60R) alteration is located in exon 2 (coding exon 1) of the TMEM171 gene. This alteration results from a A to G substitution at nucleotide position 179, causing the lysine (K) at amino acid position 60 to be replaced by an arginine (R). 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

0.21

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.29

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.46

MVP

0.46

MPC

0.37

ClinPred

0.16

GERP RS

5.2

Varity_R

0.56

gMVP

0.65

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