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

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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

GnomAD2 exomes

AF:

0.0679

AC:

16970

AN:

249978

AF XY:

0.0659

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 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

African (AFR)

AF:

0.0279

AC:

934

AN:

33476

American (AMR)

AF:

0.0898

AC:

4007

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.0174

AC:

454

AN:

26030

East Asian (EAS)

AF:

0.315

AC:

12514

AN:

39694

South Asian (SAS)

AF:

0.101

AC:

8668

AN:

86128

European-Finnish (FIN)

AF:

0.0320

AC:

1708

AN:

53380

Middle Eastern (MID)

AF:

0.0141

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0228

AC:

25324

AN:

1111370

Other (OTH)

AF:

0.0482

AC:

2906

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

2615

5230

7844

10459

13074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1236

2472

3708

4944

6180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0420

AC:

6387

AN:

152242

Hom.:

425

Cov.:

AF XY:

0.0463

AC XY:

3444

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0289

AC:

1201

AN:

41544

American (AMR)

AF:

0.0533

AC:

815

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3470

East Asian (EAS)

AF:

0.338

AC:

1746

AN:

5164

South Asian (SAS)

AF:

0.113

AC:

547

AN:

4832

European-Finnish (FIN)

AF:

0.0357

AC:

379

AN:

10602

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0229

AC:

1558

AN:

68028

Other (OTH)

AF:

0.0341

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

284

567

851

1134

1418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0275

Hom.:

233

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

(source)

DANN

Benign

0.57

PhyloP100

-3.4

PromoterAI

-0.0088

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over