Variant 1-36308183-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001162530.2(SH3D21):c.613G>C(p.Gly205Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000194 in 1,546,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SH3D21
NM_001162530.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3D21	NM_001162530.2 linkuse as main transcript	c.613G>C	p.Gly205Arg	missense_variant	8/16	ENST00000453908.8	NP_001156002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3D21	ENST00000453908.8 linkuse as main transcript	c.613G>C	p.Gly205Arg	missense_variant	8/16	5	NM_001162530.2	ENSP00000403476	P1	A4FU49-6
SH3D21	ENST00000505871.7 linkuse as main transcript	c.280G>C	p.Gly94Arg	missense_variant	5/13	2		ENSP00000421294		A4FU49-3
SH3D21	ENST00000480549.6 linkuse as main transcript	c.160-206G>C		intron_variant, NMD_transcript_variant		2		ENSP00000425484
SH3D21	ENST00000496636.1 linkuse as main transcript	n.215-206G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

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:

0.000193

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:

0.00000143

AC:

AN:

1393976

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

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:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Oct 18, 2021

The c.613G>C (p.G205R) alteration is located in exon 8 (coding exon 8) of the SH3D21 gene. This alteration results from a G to C substitution at nucleotide position 613, causing the glycine (G) at amino acid position 205 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

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Uncertain

0.36

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-7.4

D;D

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

1.0

.;D

Vest4

0.71

MVP

0.74

MPC

0.44

ClinPred

0.97

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.36

Position offset: 8

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