GeneBe

rs78120278

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024577.4(SH3TC2):ā€‹c.2235T>Gā€‹(p.Ala745=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0057 in 1,614,190 control chromosomes in the GnomAD database, including 452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.031 ( 240 hom., cov: 33)
Exomes š‘“: 0.0031 ( 212 hom. )

Consequence

SH3TC2
NM_024577.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.516
Variant links:
Genes affected
SH3TC2 (HGNC:29427): (SH3 domain and tetratricopeptide repeats 2) This gene encodes a protein with two N-terminal Src homology 3 (SH3) domains and 10 tetratricopeptide repeat (TPR) motifs, and is a member of a small gene family. The gene product has been proposed to be an adapter or docking molecule. Mutations in this gene result in autosomal recessive Charcot-Marie-Tooth disease type 4C, a childhood-onset neurodegenerative disease characterized by demyelination of motor and sensory neurons. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BP6
Variant 5-149027497-A-C is Benign according to our data. Variant chr5-149027497-A-C is described in ClinVar as [Benign]. Clinvar id is 351906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-149027497-A-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.516 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SH3TC2NM_024577.4 linkuse as main transcriptc.2235T>G p.Ala745= synonymous_variant 11/17 ENST00000515425.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SH3TC2ENST00000515425.6 linkuse as main transcriptc.2235T>G p.Ala745= synonymous_variant 11/171 NM_024577.4 P2Q8TF17-1

Frequencies

GnomAD3 genomes
AF:
0.0308
AC:
4684
AN:
152198
Hom.:
240
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.107
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0107
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000514
Gnomad OTH
AF:
0.0220
GnomAD3 exomes
AF:
0.00771
AC:
1939
AN:
251460
Hom.:
94
AF XY:
0.00577
AC XY:
784
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.104
Gnomad AMR exome
AF:
0.00520
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000425
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.00375
GnomAD4 exome
AF:
0.00309
AC:
4516
AN:
1461874
Hom.:
212
Cov.:
32
AF XY:
0.00270
AC XY:
1966
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.107
Gnomad4 AMR exome
AF:
0.00581
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000487
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000162
Gnomad4 OTH exome
AF:
0.00676
GnomAD4 genome
AF:
0.0308
AC:
4689
AN:
152316
Hom.:
240
Cov.:
33
AF XY:
0.0304
AC XY:
2268
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.107
Gnomad4 AMR
AF:
0.0107
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000514
Gnomad4 OTH
AF:
0.0218
Alfa
AF:
0.0142
Hom.:
29
Bravo
AF:
0.0349
Asia WGS
AF:
0.00779
AC:
27
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000356

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease Benign:1
Benign, criteria provided, single submitterclinical testingMolecular Genetics Laboratory, London Health Sciences Centre-- -
Charcot-Marie-Tooth disease type 4C Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Susceptibility to mononeuropathy of the median nerve, mild Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Charcot-Marie-Tooth disease type 4 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
1.2
DANN
Benign
0.40

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.

Other links and lift over

dbSNP: rs78120278; hg19: chr5-148407060; API