Variant 4-8212769-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_018986.5(SH3TC1):c.316C>T(p.Leu106Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,611,920 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 0.00012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

SH3TC1
NM_018986.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.460

Variant links:

Genes affected

SH3TC1 (HGNC:26009): (SH3 domain and tetratricopeptide repeats 1)

SH3TC1 links:

SH3TC1 (HGNC:):

SH3TC1 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=0.14981955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3TC1	NM_018986.5 linkuse as main transcript	c.316C>T	p.Leu106Phe	missense_variant	4/18	ENST00000245105.8	NP_061859.4	Q8TE82B3KWX8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3TC1	ENST00000245105.8 linkuse as main transcript	c.316C>T	p.Leu106Phe	missense_variant	4/18	2	NM_018986.5	ENSP00000245105.3		Q8TE82

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

244774

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133124

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.0000876

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000959

AC:

AN:

1459690

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726094

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.000118

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000410

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000495

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

Aug 30, 2022

The c.316C>T (p.L106F) alteration is located in exon 4 (coding exon 3) of the SH3TC1 gene. This alteration results from a C to T substitution at nucleotide position 316, causing the leucine (L) at amino acid position 106 to be replaced by a phenylalanine (F). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0064

.;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.087

LIST_S2

Uncertain

0.86

D;T

M_CAP

Benign

0.071

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.5

.;M

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.5

D;N

REVEL

Uncertain

0.40

Sift

Benign

0.077

T;T

Sift4G

Uncertain

0.042

D;T

Polyphen

0.97

.;D

Vest4

0.30

MVP

0.69

MPC

0.21

ClinPred

0.31

GERP RS

-1.0

Varity_R

0.096

gMVP

0.38

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