Variant 8-30645458-T-C 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_001206847.2(SMIM18):c.149T>C(p.Val50Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00844 in 1,535,702 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 63 hom. )

Consequence

SMIM18
NM_001206847.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.32

Variant links:

Genes affected

SMIM18 (HGNC:42973): (small integral membrane protein 18) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM18 links:

GTF2E2 (HGNC:4651): (general transcription factor IIE subunit 2) The general transcription factor IIE (TFIIE) is part of the RNA polymerase II transcription initiation complex, recruiting TFIIH and being essential for promoter clearance by RNA polymerase II. TFIIE is a heterodimer (and sometimes heterotetramer) of alpha and beta subunits. The protein encoded by this gene represents the beta subunit of TFIIE. [provided by RefSeq, Jan 2017]

GTF2E2 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=0.007305175).

BP6

Variant 8-30645458-T-C is Benign according to our data. Variant chr8-30645458-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658515.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMIM18	NM_001206847.2 linkuse as main transcript	c.149T>C	p.Val50Ala	missense_variant	3/3	ENST00000517349.2	NP_001193776.1
GTF2E2	NM_002095.6 linkuse as main transcript	c.166+7975A>G		intron_variant		ENST00000355904.9	NP_002086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMIM18	ENST00000517349.2 linkuse as main transcript	c.149T>C	p.Val50Ala	missense_variant	3/3	2	NM_001206847.2	ENSP00000428858	P1
GTF2E2	ENST00000355904.9 linkuse as main transcript	c.166+7975A>G		intron_variant		1	NM_002095.6	ENSP00000348168	P1

Frequencies

GnomAD3 genomes

AF:

0.00559

AC:

851

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00920

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00539

AC:

692

AN:

128392

Hom.:

AF XY:

0.00546

AC XY:

384

AN XY:

70314

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.000741

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00393

Gnomad FIN exome

AF:

0.00483

Gnomad NFE exome

AF:

0.00988

Gnomad OTH exome

AF:

0.00450

GnomAD4 exome

AF:

0.00876

AC:

12118

AN:

1383352

Hom.:

Cov.:

AF XY:

0.00856

AC XY:

5844

AN XY:

682578

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.000635

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00329

Gnomad4 FIN exome

AF:

0.00556

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.00717

GnomAD4 genome

AF:

0.00558

AC:

850

AN:

152350

Hom.:

Cov.:

AF XY:

0.00519

AC XY:

387

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.00920

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00585

Hom.:

Bravo

AF:

0.00541

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.00908

AC:

ExAC

AF:

0.00260

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

SMIM18: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0073

MetaSVM

Benign

-0.85

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.11

MVP

0.095

ClinPred

0.16

GERP RS

4.5

Varity_R

0.47

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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