Variant 19-55383830-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000444469.4(TMEM238):c.430G>T(p.Ala144Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 635,414 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00046 ( 2 hom. )

Consequence

TMEM238
ENST00000444469.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.495

Variant links:

Genes affected

TMEM238 (HGNC:40042): (transmembrane protein 238) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM238 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02818796).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM238	NM_001190764.2 linkuse as main transcript	c.430G>T	p.Ala144Ser	missense_variant	1/2	ENST00000444469.4	NP_001177693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM238	ENST00000444469.4 linkuse as main transcript	c.430G>T	p.Ala144Ser	missense_variant	1/2	1	NM_001190764.2	ENSP00000416154	P1

Frequencies

GnomAD3 genomes

AF:

0.000288

AC:

AN:

145710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000737

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000424

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000533

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000464

AC:

227

AN:

489628

Hom.:

Cov.:

AF XY:

0.000397

AC XY:

AN XY:

229252

show subpopulations

Gnomad4 AFR exome

AF:

0.000328

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000326

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000101

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000478

Gnomad4 OTH exome

AF:

0.000372

GnomAD4 genome

AF:

0.000288

AC:

AN:

145786

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

AN XY:

70926

show subpopulations

Gnomad4 AFR

AF:

0.0000735

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000424

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000533

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000336

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.430G>T (p.A144S) alteration is located in exon 1 (coding exon 1) of the TMEM238 gene. This alteration results from a G to T substitution at nucleotide position 430, causing the alanine (A) at amino acid position 144 to be replaced by a serine (S). 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

0.072

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.7

DANN

Benign

0.94

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.31

M_CAP

Benign

0.033

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.17

REVEL

Benign

0.018

Sift

Benign

0.57

Sift4G

Benign

0.48

Polyphen

0.029

Vest4

0.050

MutPred

0.18

Gain of phosphorylation at A144 (P = 2e-04);

MVP

0.014

ClinPred

0.054

GERP RS

-5.3

Varity_R

0.035

gMVP

0.13

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

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