Variant 18-75427512-C-T 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_001037331.3(SMIM21):c.52G>A(p.Gly18Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SMIM21
NM_001037331.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.195

Variant links:

Genes affected

SMIM21 (HGNC:27598): (small integral membrane protein 21) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SMIM21 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=0.08841571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMIM21	NM_001037331.3 link	c.52G>A	p.Gly18Arg	missense_variant	1/3	ENST00000579022.5	NP_001032408.1	Q3B7S5
SMIM21	NM_001303482.2 link	c.52G>A	p.Gly18Arg	missense_variant	1/3		NP_001290411.1	J3KSN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMIM21	ENST00000579022.5 link	c.52G>A	p.Gly18Arg	missense_variant	1/3	1	NM_001037331.3	ENSP00000462106.1	Q3B7S5
SMIM21	ENST00000584508.1 link	c.52G>A	p.Gly18Arg	missense_variant	1/3	1		ENSP00000462572.1	J3KSN8
SMIM21	ENST00000382638.3 link	c.52G>A	p.Gly18Arg	missense_variant	1/2	1		ENSP00000372083.3	J9JIF2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251176

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135756

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

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

May 25, 2022

The c.52G>A (p.G18R) alteration is located in exon 1 (coding exon 1) of the SMIM21 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the glycine (G) at amino acid position 18 to be replaced by an arginine (R). 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

0.33

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.34

DEOGEN2

Benign

0.10

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.088

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-7.4

.;D;.

REVEL

Benign

0.060

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.13

B;.;.

Vest4

0.18

MutPred

0.27

Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);

MVP

0.014

MPC

0.67

ClinPred

0.098

GERP RS

-1.8

Varity_R

0.24

gMVP

0.0024

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