4-8205583-G-A

Position:

• chr4-8205583-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The ENST00000382521.7(SH3TC1):​c.219G>A​(p.Ser73Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 797,802 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: SH3TC1 ENST00000382521.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.152

Genes affected

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

SH3TC1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-8205583-G-A is Benign according to our data. Variant chr4-8205583-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654645.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.152 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3TC1	NM_018986.5	c.172+217G>A		intron_variant		ENST00000245105.8	NP_061859.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3TC1	ENST00000245105.8	c.172+217G>A		intron_variant		2	NM_018986.5	ENSP00000245105.3

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00176

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00115 AC: 264 AN: 229922 Hom.: 0 AF XY: 0.00123 AC XY: 156 AN XY: 127136

Gnomad AFR exome AF: 0.0000714

Gnomad AMR exome AF: 0.000379

Gnomad ASJ exome AF: 0.00507

Gnomad EAS exome AF: 0.000113

Gnomad SAS exome AF: 0.000165

Gnomad FIN exome AF: 0.0000850

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.00204

GnomAD4 exome AF: 0.00120 AC: 775 AN: 645460 Hom.: 1 Cov.: 7 AF XY: 0.00114 AC XY: 399 AN XY: 350954

Gnomad4 AFR exome AF: 0.0000550

Gnomad4 AMR exome AF: 0.000388

Gnomad4 ASJ exome AF: 0.00463

Gnomad4 EAS exome AF: 0.0000552

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.000132

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.00191

GnomAD4 genome AF: 0.00110 AC: 167 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000993 AC XY: 74 AN XY: 74488

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00176

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00165 Hom.: 0

Bravo AF: 0.00111

EpiCase AF: 0.00196

EpiControl AF: 0.00249

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SH3TC1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs199884098; hg19: chr4-8207310;