Variant 1-36309567-G-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_001162530.2(SH3D21):c.746G>A(p.Arg249Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,551,646 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

SH3D21
NM_001162530.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

Variant links:

Genes affected

SH3D21 (HGNC:26236): (SH3 domain containing 21) Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SH3D21 links:

SH3D21 (HGNC:):

SH3D21 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=0.09702605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3D21	NM_001162530.2 linkuse as main transcript	c.746G>A	p.Arg249Gln	missense_variant	10/16	ENST00000453908.8	NP_001156002.1	A4FU49-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SH3D21	ENST00000453908.8 linkuse as main transcript	c.746G>A	p.Arg249Gln	missense_variant	10/16	5	NM_001162530.2	ENSP00000403476.2	A4FU49-6
SH3D21	ENST00000505871.7 linkuse as main transcript	c.413G>A	p.Arg138Gln	missense_variant	7/13	2		ENSP00000421294.1	A4FU49-3
SH3D21	ENST00000480549.6 linkuse as main transcript	n.266G>A		non_coding_transcript_exon_variant	5/12	2		ENSP00000425484.1	D6RD64
SH3D21	ENST00000496636.1 linkuse as main transcript	n.358G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152182

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000769

AC:

AN:

155960

Hom.:

AF XY:

0.0000967

AC XY:

AN XY:

82704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

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:

0.000166

Gnomad OTH exome

AF:

0.000228

GnomAD4 exome

AF:

0.000237

AC:

332

AN:

1399346

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

162

AN XY:

690182

show subpopulations

Gnomad4 AFR exome

AF:

0.000127

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000252

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000282

Gnomad4 OTH exome

AF:

0.000345

GnomAD4 genome

AF:

0.000112

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74472

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:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.0000381

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Apr 26, 2024

The c.746G>A (p.R249Q) alteration is located in exon 10 (coding exon 10) of the SH3D21 gene. This alteration results from a G to A substitution at nucleotide position 746, causing the arginine (R) at amino acid position 249 to be replaced by a glutamine (Q). 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

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.097

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.090

Sift

Benign

0.030

D;D

Sift4G

Benign

0.20

T;T

Polyphen

1.0

.;D

Vest4

0.16

MVP

0.32

MPC

0.42

ClinPred

0.37

GERP RS

4.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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