5-148983225-CGTTT-C

Position:

• chr5-148983225-CGTTT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_024577.4(SH3TC2):​c.*21482_*21485del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 152,232 control chromosomes in the GnomAD database, including 339 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.035 (339 hom., cov: 32)
• Consequence: SH3TC2 NM_024577.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.541

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 5-148983225-CGTTT-C is Benign according to our data. Variant chr5-148983225-CGTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 351579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3TC2	NM_024577.4	c.*21482_*21485del		3_prime_UTR_variant	17/17	ENST00000515425.6	NP_078853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3TC2	ENST00000515425.6	c.*21482_*21485del		3_prime_UTR_variant	17/17	1	NM_024577.4	ENSP00000423660	P2
SH3TC2	ENST00000504690.5	c.*12+20497_*12+20500del		intron_variant, NMD_transcript_variant		5		ENSP00000425627
SH3TC2	ENST00000510350.1	n.231+23652_231+23655del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5268 AN: 152114 Hom.: 336 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0459

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0347 AC: 5280 AN: 152232 Hom.: 339 Cov.: 32 AF XY: 0.0377 AC XY: 2807 AN XY: 74430

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0567

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.0179

Gnomad4 OTH AF: 0.0469

Alfa AF: 0.0244 Hom.: 26

Bravo AF: 0.0474

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mononeuropathy of the Median Nerve Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Charcot-Marie-Tooth disease type 4 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146796490; hg19: chr5-148362788;