Variant 6-87337035-T-A 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_001042493.3(SMIM8):c.4T>A(p.Ser2Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,598,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

SMIM8
NM_001042493.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

Variant links:

Genes affected

SMIM8 (HGNC:21401): (small integral membrane protein 8) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM8 links:

Genome browser will be placed here

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=0.15353453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMIM8	NM_001042493.3 linkuse as main transcript	c.4T>A	p.Ser2Thr	missense_variant	3/4	ENST00000392863.6
SMIM8	NM_020425.6 linkuse as main transcript	c.4T>A	p.Ser2Thr	missense_variant	2/3
SMIM8	NM_001287445.2 linkuse as main transcript	c.4T>A	p.Ser2Thr	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM8	ENST00000392863.6 linkuse as main transcript	c.4T>A	p.Ser2Thr	missense_variant	3/4	1	NM_001042493.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152178

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000206

AC:

AN:

242622

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

131076

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000449

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1445964

Hom.:

Cov.:

AF XY:

0.0000376

AC XY:

AN XY:

718570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000390

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000352

Gnomad4 OTH exome

AF:

0.0000671

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

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 13, 2024

The c.4T>A (p.S2T) alteration is located in exon 3 (coding exon 1) of the SMIM8 gene. This alteration results from a T to A substitution at nucleotide position 4, causing the serine (S) at amino acid position 2 to be replaced by a threonine (T). 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

0.078

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0062

T;T;T;T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.60

.;T;.;T;.

M_CAP

Benign

0.0083

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.50

.;N;N;.;.

REVEL

Benign

0.081

Sift

Uncertain

0.019

.;D;D;.;.

Sift4G

Benign

0.077

T;T;T;D;T

Polyphen

0.14

B;B;B;.;B

Vest4

0.42

MutPred

0.29

Gain of glycosylation at S2 (P = 0.0158);Gain of glycosylation at S2 (P = 0.0158);Gain of glycosylation at S2 (P = 0.0158);Gain of glycosylation at S2 (P = 0.0158);Gain of glycosylation at S2 (P = 0.0158);

MVP

0.014

MPC

0.22

ClinPred

0.71

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.72

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