chr5-148982157-A-AT

Position:

• chr5-148982157-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024577.4(SH3TC2):​c.*22553_*22554insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.49 (18753 hom., cov: 0)
• Consequence: SH3TC2 NM_024577.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.00

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 -10 ACMG points.

• BP6: Variant 5-148982157-A-AT is Benign according to our data. Variant chr5-148982157-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 351562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3TC2	NM_024577.4	c.*22553_*22554insA		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.*22553_*22554insA		3_prime_UTR_variant	17/17	1	NM_024577.4	ENSP00000423660	P2
SH3TC2	ENST00000504690.5	c.*12+21568_*12+21569insA		intron_variant, NMD_transcript_variant		5		ENSP00000425627
SH3TC2	ENST00000510350.1	n.231+24723_231+24724insA		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 73720 AN: 150228 Hom.: 18751 Cov.: 0

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.490 AC: 73729 AN: 150332 Hom.: 18753 Cov.: 0 AF XY: 0.486 AC XY: 35634 AN XY: 73352

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.499

Bravo AF: 0.481

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

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

- -

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: rs55932017; hg19: chr5-148361720;