rs80227512

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_024577.4(SH3TC2):c.645C>T(p.Ser215Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00908 in 1,614,160 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0065 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0093 ( 101 hom. )

Consequence

SH3TC2
NM_024577.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: -1.79

Publications

3 publications found

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]

SH3TC2 Gene-Disease associations (from GenCC):

autosomal recessive hereditary demyelinating motor and sensory neuropathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Charcot-Marie-Tooth disease type 4C
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
susceptibility to mononeuropathy of the median nerve, mild
Inheritance: AD, AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia

SH3TC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-149041502-G-A is Benign according to our data. Variant chr5-149041502-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 130301.

BP7

Synonymous conserved (PhyloP=-1.79 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00651 (992/152302) while in subpopulation SAS AF = 0.0226 (109/4830). AF 95% confidence interval is 0.0191. There are 5 homozygotes in GnomAd4. There are 453 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024577.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3TC2	NM_024577.4	MANE Select	c.645C>T	p.Ser215Ser	synonymous	Exon 6 of 17	NP_078853.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3TC2	ENST00000515425.6	TSL:1 MANE Select	c.645C>T	p.Ser215Ser	synonymous	Exon 6 of 17	ENSP00000423660.1	Q8TF17-1
SH3TC2	ENST00000512049.5	TSL:1	c.624C>T	p.Ser208Ser	synonymous	Exon 6 of 17	ENSP00000421860.1	Q8TF17-5
SH3TC2	ENST00000323829.9	TSL:1	n.645C>T		non_coding_transcript_exon	Exon 6 of 18	ENSP00000313025.5	D6RA65

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

992

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0225

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00935

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00907

AC:

2279

AN:

251280

AF XY:

0.0103

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.0170

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00481

Gnomad NFE exome

AF:

0.00990

Gnomad OTH exome

AF:

0.00963

GnomAD4 exome

AF:

0.00935

AC:

13667

AN:

1461858

Hom.:

101

Cov.:

AF XY:

0.00994

AC XY:

7225

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

33480

American (AMR)

AF:

0.00387

AC:

173

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0145

AC:

379

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0220

AC:

1898

AN:

86256

European-Finnish (FIN)

AF:

0.00539

AC:

288

AN:

53416

Middle Eastern (MID)

AF:

0.0125

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00925

AC:

10288

AN:

1112010

Other (OTH)

AF:

0.00861

AC:

520

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

877

1754

2630

3507

4384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

406

812

1218

1624

2030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00651

AC:

992

AN:

152302

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

453

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

41556

American (AMR)

AF:

0.00418

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0226

AC:

109

AN:

4830

European-Finnish (FIN)

AF:

0.00377

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00935

AC:

636

AN:

68020

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

110

164

219

274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00655

Hom.:

Bravo

AF:

0.00591

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.00998

EpiControl

AF:

0.0116

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Charcot-Marie-Tooth disease (1)

Charcot-Marie-Tooth disease type 4 (1)

Charcot-Marie-Tooth disease type 4C (1)

Inborn genetic diseases (1)

not specified (1)

Susceptibility to mononeuropathy of the median nerve, mild (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.56

(source)

DANN

Benign

0.43

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over