Variant 2-672826-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152834.4(TMEM18):c.215C>T(p.Ala72Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,479,316 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 3 hom. )

Consequence

TMEM18
NM_152834.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

TMEM18 (HGNC:25257): (transmembrane protein 18) Predicted to enable DNA binding activity. Involved in cell migration. Located in nuclear membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015538156).

BP6

Variant 2-672826-G-A is Benign according to our data. Variant chr2-672826-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2400369.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM18	NM_152834.4 linkuse as main transcript	c.215C>T	p.Ala72Val	missense_variant	3/5	ENST00000281017.8	NP_690047.2
TMEM18	NM_001352681.1 linkuse as main transcript	c.224C>T	p.Ala75Val	missense_variant	3/5		NP_001339610.1
TMEM18	NM_001352680.2 linkuse as main transcript	c.176C>T	p.Ala59Val	missense_variant	4/6		NP_001339609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM18	ENST00000281017.8 linkuse as main transcript	c.215C>T	p.Ala72Val	missense_variant	3/5	1	NM_152834.4	ENSP00000281017	P1	Q96B42-1

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000623

AC:

AN:

158986

Hom.:

AF XY:

0.000543

AC XY:

AN XY:

88420

show subpopulations

Gnomad AFR exome

AF:

0.0000964

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.000165

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000305

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000633

GnomAD4 exome

AF:

0.000500

AC:

664

AN:

1327000

Hom.:

Cov.:

AF XY:

0.000529

AC XY:

345

AN XY:

651850

show subpopulations

Gnomad4 AFR exome

AF:

0.0000385

Gnomad4 AMR exome

AF:

0.000103

Gnomad4 ASJ exome

AF:

0.0000457

Gnomad4 EAS exome

AF:

0.0000320

Gnomad4 SAS exome

AF:

0.0000153

Gnomad4 FIN exome

AF:

0.000366

Gnomad4 NFE exome

AF:

0.000590

Gnomad4 OTH exome

AF:

0.000330

GnomAD4 genome

AF:

0.000525

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000891

Hom.:

Bravo

AF:

0.000408

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000544

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 07, 2022

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

0.049

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.7

DANN

Benign

0.63

DEOGEN2

Benign

0.0077

T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.1

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

1.5

N;N;N

REVEL

Benign

0.035

Sift

Benign

0.81

T;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.0040

B;.;.

Vest4

0.25

MVP

0.081

MPC

0.15

ClinPred

0.0035

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.011

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over