Genetic Variant TMEM161A:p.Thr143Thr (chr19-19132366-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017814.3(TMEM161A):c.429G>A(p.Thr143Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,613,058 control chromosomes in the GnomAD database, including 3,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.042 ( 425 hom., cov: 33)

Exomes 𝑓: 0.039 ( 3291 hom. )

Consequence

TMEM161A
NM_017814.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.36

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP7

Synonymous conserved (PhyloP=-3.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM161A	NM_017814.3 link	c.429G>A	p.Thr143Thr	synonymous_variant	Exon 5 of 12	ENST00000162044.14	NP_060284.1	Q9NX61-1
TMEM161A	NM_001411131.1 link	c.354G>A	p.Thr118Thr	synonymous_variant	Exon 5 of 12		NP_001398060.1
TMEM161A	XM_047439023.1 link	c.378G>A	p.Thr126Thr	synonymous_variant	Exon 5 of 12		XP_047294979.1
TMEM161A	NM_001256766.3 link	c.286+291G>A		intron_variant	Intron 4 of 9		NP_001243695.1	Q9NX61-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM161A	ENST00000162044.14 link	c.429G>A	p.Thr143Thr	synonymous_variant	Exon 5 of 12	1	NM_017814.3	ENSP00000162044.7		Q9NX61-1

Frequencies

GnomAD3 genomes

AF:

0.0420

AC:

6383

AN:

152122

Hom.:

425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0287

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0534

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0357

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0229

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0679

AC:

16970

AN:

249978

Hom.:

1559

AF XY:

0.0659

AC XY:

8894

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.0953

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.352

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0331

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0458

GnomAD4 exome

AF:

0.0387

AC:

56596

AN:

1460816

Hom.:

3291

Cov.:

AF XY:

0.0400

AC XY:

29065

AN XY:

726716

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.0898

Gnomad4 ASJ exome

AF:

0.0174

Gnomad4 EAS exome

AF:

0.315

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0320

Gnomad4 NFE exome

AF:

0.0228

Gnomad4 OTH exome

AF:

0.0482

GnomAD4 genome

AF:

0.0420

AC:

6387

AN:

152242

Hom.:

425

Cov.:

AF XY:

0.0463

AC XY:

3444

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0289

Gnomad4 AMR

AF:

0.0533

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.338

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0357

Gnomad4 NFE

AF:

0.0229

Gnomad4 OTH

AF:

0.0341

Alfa

AF:

0.0274

Hom.:

183

Bravo

AF:

0.0438

Asia WGS

AF:

0.195

AC:

679

AN:

3478

EpiCase

AF:

0.0195

EpiControl

AF:

0.0189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.45

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over