Variant X-154830732-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001162936.4(SMIM9):c.125C>T(p.Ser42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000764 in 1,165,563 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000083 ( 0 hom. 30 hem. )

Consequence

SMIM9
NM_001162936.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.25

Variant links:

Genes affected

SMIM9 (HGNC:41915): (small integral membrane protein 9) Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM9 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=0.01904586).

BS2

High Hemizygotes in GnomAdExome at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMIM9	NM_001162936.4 linkuse as main transcript	c.125C>T	p.Ser42Leu	missense_variant	3/5	ENST00000369529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMIM9	ENST00000369529.2 linkuse as main transcript	c.125C>T	p.Ser42Leu	missense_variant	3/5	5	NM_001162936.4	P1
SMIM9	ENST00000478043.1 linkuse as main transcript	n.434C>T		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111550

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33754

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:

0.000556

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

GnomAD3 exomes

AF:

0.0000966

AC:

AN:

113905

Hom.:

AF XY:

0.0000998

AC XY:

AN XY:

40091

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00124

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000825

AC:

AN:

1053957

Hom.:

Cov.:

AF XY:

0.0000871

AC XY:

AN XY:

344453

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00306

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000366

Gnomad4 OTH exome

AF:

0.0000225

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111606

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33820

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000558

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000264

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

Jul 27, 2022

The c.125C>T (p.S42L) alteration is located in exon 3 (coding exon 1) of the SMIM9 gene. This alteration results from a C to T substitution at nucleotide position 125, causing the serine (S) at amino acid position 42 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

Benign

0.079

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-1.1

Cadd

Benign

0.0060

Dann

Benign

0.80

DEOGEN2

Benign

0.023

FATHMM_MKL

Benign

0.0059

LIST_S2

Benign

0.47

M_CAP

Benign

0.0011

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.94

REVEL

Benign

0.079

Sift

Benign

0.12

Sift4G

Benign

0.49

Vest4

0.028

MVP

0.072

ClinPred

0.029

GERP RS

-4.9

Varity_R

0.041

gMVP

0.023

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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