dbSNP rs923774959: TMEM160:p.Ala38Thr (chr19-47048503-C-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_017854.2(TMEM160):c.112G>A(p.Ala38Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000852 in 1,291,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000085 ( 0 hom. )

Consequence

TMEM160
NM_017854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.872

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: 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=0.124337345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2 link	c.112G>A	p.Ala38Thr	missense_variant	Exon 1 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.112G>A	p.Ala38Thr	missense_variant	Exon 1 of 3	1	NM_017854.2	ENSP00000253047.5		Q9NX00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000194

AC:

AN:

51494

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:

0.0000485

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000852

AC:

AN:

1291510

Hom.:

Cov.:

AF XY:

0.00000473

AC XY:

AN XY:

633988

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25184

American (AMR)

AF:

0.00

AC:

AN:

19122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20486

East Asian (EAS)

AF:

0.00

AC:

AN:

29640

South Asian (SAS)

AF:

0.00

AC:

AN:

67872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31472

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3718

European-Non Finnish (NFE)

AF:

0.0000106

AC:

AN:

1040586

Other (OTH)

AF:

0.00

AC:

AN:

53430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 20, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.112G>A (p.A38T) alteration is located in exon 1 (coding exon 1) of the TMEM160 gene. This alteration results from a G to A substitution at nucleotide position 112, causing the alanine (A) at amino acid position 38 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0088

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.61

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

0.87

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.85

REVEL

Benign

0.032

Sift

Uncertain

0.011

Sift4G

Benign

0.13

Polyphen

0.55

Vest4

0.17

MutPred

0.20

Gain of phosphorylation at A38 (P = 0.0015);

MVP

0.082

MPC

1.1

ClinPred

0.23

GERP RS

2.2

PromoterAI

0.029

Neutral

(source)

Varity_R

0.12

gMVP

0.47

Mutation Taster

=97/3

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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rs923774959

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over