Variant 19-55384022-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001190764.2(TMEM238):c.238T>C(p.Phe80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000404 in 1,483,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

TMEM238
NM_001190764.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.734

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35168576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM238	NM_001190764.2 link	c.238T>C	p.Phe80Leu	missense_variant	1/2	ENST00000444469.4	NP_001177693.1	C9JI98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM238	ENST00000444469.4 link	c.238T>C	p.Phe80Leu	missense_variant	1/2	1	NM_001190764.2	ENSP00000416154.2		C9JI98

Frequencies

GnomAD3 genomes

AF:

0.00000674

AC:

AN:

148394

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:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000374

AC:

AN:

1335162

Hom.:

Cov.:

AF XY:

0.00000455

AC XY:

AN XY:

659152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000154

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000674

AC:

AN:

148394

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72280

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Feb 28, 2023

The c.238T>C (p.F80L) alteration is located in exon 1 (coding exon 1) of the TMEM238 gene. This alteration results from a T to C substitution at nucleotide position 238, causing the phenylalanine (F) at amino acid position 80 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

Pathogenic

1.0

BayesDel_addAF

Benign

-0.0075

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.15

Eigen

Benign

0.070

Eigen_PC

Benign

-0.011

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.3

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.26

Sift

Benign

0.21

Sift4G

Benign

0.29

Polyphen

0.99

Vest4

0.46

MutPred

0.36

Loss of catalytic residue at F80 (P = 0.2304);

MVP

0.085

ClinPred

0.28

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.23

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