Genetic Variant NM_017814.3:c.1216C>T (chr19-19120154-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017814.3(TMEM161A):c.1216C>T(p.Pro406Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000874 in 1,558,892 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P406A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00046 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00092 ( 11 hom. )

Consequence

TMEM161A
NM_017814.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.789

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040674806).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM161A	NM_017814.3 link	c.1216C>T	p.Pro406Ser	missense_variant	Exon 12 of 12	ENST00000162044.14	NP_060284.1	Q9NX61-1
TMEM161A	NM_001411131.1 link	c.1141C>T	p.Pro381Ser	missense_variant	Exon 12 of 12		NP_001398060.1
TMEM161A	NM_001256766.3 link	c.907C>T	p.Pro303Ser	missense_variant	Exon 10 of 10		NP_001243695.1	Q9NX61-2
TMEM161A	XM_047439023.1 link	c.1165C>T	p.Pro389Ser	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.1216C>T	p.Pro406Ser	missense_variant	Exon 12 of 12	1	NM_017814.3	ENSP00000162044.7		Q9NX61-1

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00223

AC:

366

AN:

164414

AF XY:

0.00323

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000396

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000219

GnomAD4 exome

AF:

0.000919

AC:

1293

AN:

1406738

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

937

AN XY:

694204

show subpopulations

African (AFR)

AF:

0.0000308

AC:

AN:

32452

American (AMR)

AF:

0.0000551

AC:

AN:

36284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25106

East Asian (EAS)

AF:

0.0000808

AC:

AN:

37148

South Asian (SAS)

AF:

0.0152

AC:

1220

AN:

80020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49118

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5504

European-Non Finnish (NFE)

AF:

0.00000646

AC:

AN:

1082810

Other (OTH)

AF:

0.00101

AC:

AN:

58296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

144

217

289

361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000460

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000780

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41496

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.0145

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.00182

AC:

212

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.6

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.023

.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

.;N;.

PhyloP100

0.79

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.91

N;N;.

REVEL

Benign

0.056

Sift

Benign

0.50

T;T;.

Sift4G

Benign

0.15

T;T;T

Polyphen

0.0060

.;B;.

Vest4

0.048

MutPred

0.46

.;Gain of glycosylation at P406 (P = 0.0464);.;

MVP

0.085

MPC

0.25

ClinPred

0.021

GERP RS

-3.9

Varity_R

0.023

gMVP

0.12

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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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NM_017814.3:c.1216C>T

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