Variant 19-19121640-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017814.3(TMEM161A):c.685G>T(p.Val229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

TMEM161A
NM_017814.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.944

Variant links:

Genes affected

TMEM161A (HGNC:26020): (transmembrane protein 161A) Involved in several processes, including cellular response to UV; regulation of response to DNA damage stimulus; and response to retinoic acid. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM161A links:

TMEM161A (HGNC:):

TMEM161A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058020145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM161A	NM_017814.3 linkuse as main transcript	c.685G>T	p.Val229Leu	missense_variant	8/12	ENST00000162044.14	NP_060284.1	Q9NX61-1
TMEM161A	NM_001411131.1 linkuse as main transcript	c.610G>T	p.Val204Leu	missense_variant	8/12		NP_001398060.1
TMEM161A	NM_001256766.3 linkuse as main transcript	c.376G>T	p.Val126Leu	missense_variant	6/10		NP_001243695.1	Q9NX61-2
TMEM161A	XM_047439023.1 linkuse as main transcript	c.634G>T	p.Val212Leu	missense_variant	8/12		XP_047294979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM161A	ENST00000162044.14 linkuse as main transcript	c.685G>T	p.Val229Leu	missense_variant	8/12	1	NM_017814.3	ENSP00000162044.7		Q9NX61-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250200

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461586

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 26, 2021

The c.685G>T (p.V229L) alteration is located in exon 8 (coding exon 8) of the TMEM161A gene. This alteration results from a G to T substitution at nucleotide position 685, causing the valine (V) at amino acid position 229 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

Benign

0.093

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.7

DANN

Benign

0.56

DEOGEN2

Benign

0.014

.;T;T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.70

T;T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.058

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.14

.;N;.;.;.

PrimateAI

Benign

0.34

PROVEAN

Benign

0.66

N;N;.;.;.

REVEL

Benign

0.015

Sift

Benign

0.54

T;T;.;.;.

Sift4G

Benign

1.0

T;T;T;T;.

Polyphen

0.0

.;B;.;.;.

Vest4

0.25

MutPred

0.30

.;Loss of MoRF binding (P = 0.0964);.;.;.;

MVP

0.27

MPC

0.24

ClinPred

0.011

GERP RS

-1.3

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.022

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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