Genetic Variant TMEM160:p.Arg12Leu (chr19-47048580-C-A) – 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.35G>T(p.Arg12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000065 in 1,523,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

TMEM160
NM_017854.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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:

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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=0.13466498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM160	NM_017854.2 link	c.35G>T	p.Arg12Leu	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.35G>T	p.Arg12Leu	missense_variant	Exon 1 of 3	1	NM_017854.2	ENSP00000253047.5		Q9NX00

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152174

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000655

AC:

AN:

122196

AF XY:

0.0000289

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000136

Gnomad EAS exome

AF:

0.000242

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000649

AC:

AN:

1370906

Hom.:

Cov.:

AF XY:

0.0000723

AC XY:

AN XY:

677782

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28596

American (AMR)

AF:

0.00

AC:

AN:

34974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24362

East Asian (EAS)

AF:

0.0000605

AC:

AN:

33044

South Asian (SAS)

AF:

0.00

AC:

AN:

78168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4012

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

1076752

Other (OTH)

AF:

0.000105

AC:

AN:

56992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000271

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 27, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.35G>T (p.R12L) alteration is located in exon 1 (coding exon 1) of the TMEM160 gene. This alteration results from a G to T substitution at nucleotide position 35, causing the arginine (R) at amino acid position 12 to be replaced by a leucine (L). 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

0.18

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.15

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.64

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.5

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.2

REVEL

Benign

0.079

Sift

Benign

0.080

Sift4G

Benign

0.36

Polyphen

0.23

Vest4

0.44

MutPred

0.42

Loss of methylation at R12 (P = 0.0159);

MVP

0.15

MPC

1.8

ClinPred

0.15

GERP RS

3.4

PromoterAI

0.030

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.30

Mutation Taster

=87/13

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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19-47048580-C-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