Variant chr8-30645362-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001206847.2(SMIM18):c.53G>C(p.Gly18Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000456 in 1,535,640 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SMIM18
NM_001206847.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17436695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMIM18	NM_001206847.2 linkuse as main transcript	c.53G>C	p.Gly18Ala	missense_variant	3/3	ENST00000517349.2	NP_001193776.1
GTF2E2	NM_002095.6 linkuse as main transcript	c.166+8071C>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.53G>C	p.Gly18Ala	missense_variant	3/3	2	NM_001206847.2	ENSP00000428858	P1
GTF2E2	ENST00000355904.9 linkuse as main transcript	c.166+8071C>G		intron_variant		1	NM_002095.6	ENSP00000348168	P1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1383350

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

682572

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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:

0.0000328

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

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

Nov 30, 2022

The c.53G>C (p.G18A) alteration is located in exon 3 (coding exon 1) of the SMIM18 gene. This alteration results from a G to C substitution at nucleotide position 53, causing the glycine (G) at amino acid position 18 to be replaced by an alanine (A). 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

0.15

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0044

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.81

M_CAP

Benign

0.024

MetaRNN

Benign

0.17

MetaSVM

Uncertain

-0.25

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.5

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.14

MutPred

0.38

Loss of sheet (P = 0.0011);

MVP

0.16

ClinPred

0.90

GERP RS

5.7

Varity_R

0.53

gMVP

0.38

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