Genetic Variant NM_017854.2:c.352G>A (chr19-47046202-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017854.2(TMEM160):c.352G>A(p.Ala118Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,529,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TMEM160
NM_017854.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.242

Publications

0 publications found

Variant links:

Genes affected

TMEM160 (HGNC:26042): (transmembrane protein 160) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM160 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043420106).

BP6

Variant 19-47046202-C-T is Benign according to our data. Variant chr19-47046202-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3457898.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2 link	c.352G>A	p.Ala118Thr	missense_variant	Exon 3 of 3	ENST00000253047.7	NP_060324.1	Q9NX00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM160	ENST00000253047.7 link	c.352G>A	p.Ala118Thr	missense_variant	Exon 3 of 3	1	NM_017854.2	ENSP00000253047.5		Q9NX00

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152136

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000805

AC:

AN:

124278

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000217

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1377142

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

680088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30922

American (AMR)

AF:

0.00

AC:

AN:

34212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24782

East Asian (EAS)

AF:

0.00

AC:

AN:

34892

South Asian (SAS)

AF:

0.00

AC:

AN:

78594

European-Finnish (FIN)

AF:

0.0000280

AC:

AN:

35652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4138

European-Non Finnish (NFE)

AF:

0.0000158

AC:

AN:

1076578

Other (OTH)

AF:

0.00

AC:

AN:

57372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000587

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000106

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 01, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.58

M_CAP

Benign

0.016

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

-0.24

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.2

REVEL

Benign

0.034

Sift

Benign

0.26

Sift4G

Benign

0.21

Polyphen

0.021

Vest4

0.074

MutPred

0.29

Loss of helix (P = 0.0376);

MVP

0.068

MPC

0.99

ClinPred

0.079

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.035

gMVP

0.29

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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_017854.2:c.352G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over