Genetic Variant TMEM161A:p.Leu407Ile (chr19-19120151-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017814.3(TMEM161A):c.1219C>A(p.Leu407Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMEM161A
NM_017814.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.115

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

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=0.1071271).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM161A	NM_017814.3 link	c.1219C>A	p.Leu407Ile	missense_variant	Exon 12 of 12	ENST00000162044.14	NP_060284.1	Q9NX61-1
TMEM161A	NM_001411131.1 link	c.1144C>A	p.Leu382Ile	missense_variant	Exon 12 of 12		NP_001398060.1
TMEM161A	NM_001256766.3 link	c.910C>A	p.Leu304Ile	missense_variant	Exon 10 of 10		NP_001243695.1	Q9NX61-2
TMEM161A	XM_047439023.1 link	c.1168C>A	p.Leu390Ile	missense_variant	Exon 12 of 12		XP_047294979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM161A	ENST00000162044.14 link	c.1219C>A	p.Leu407Ile	missense_variant	Exon 12 of 12	1	NM_017814.3	ENSP00000162044.7		Q9NX61-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1407602

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694742

African (AFR)

AF:

0.00

AC:

AN:

32452

American (AMR)

AF:

0.00

AC:

AN:

36348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25124

East Asian (EAS)

AF:

0.00

AC:

AN:

37198

South Asian (SAS)

AF:

0.00

AC:

AN:

80076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083392

Other (OTH)

AF:

0.00

AC:

AN:

58342

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 23, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1219C>A (p.L407I) alteration is located in exon 12 (coding exon 12) of the TMEM161A gene. This alteration results from a C to A substitution at nucleotide position 1219, causing the leucine (L) at amino acid position 407 to be replaced by an isoleucine (I). 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

0.075

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.48

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.014

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;.

PhyloP100

-0.12

PrimateAI

Benign

0.30

PROVEAN

Benign

0.12

N;N;.

REVEL

Benign

0.17

Sift

Benign

0.48

T;T;.

Sift4G

Benign

0.56

T;T;T

Polyphen

0.0030

.;B;.

Vest4

0.090

MutPred

0.42

.;Loss of catalytic residue at L407 (P = 0.0291);.;

MVP

0.085

MPC

0.28

ClinPred

0.031

GERP RS

-5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.15

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over