rs753975938

Variant names:

• chr5-149062977-C-G
• rs753975938
• NM_024577.4:c.46G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-149062977-C-G
• chr5-149062977-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000515425.6(SH3TC2):​c.46G>C​(p.Gly16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G16S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH3TC2 ENST00000515425.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 2 publications found

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-DT (HGNC:52905): (SH3TC2 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24442095).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000515425.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3TC2	NM_024577.4	MANE Select	c.46G>C	p.Gly16Arg	missense	Exon 1 of 17	NP_078853.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3TC2	ENST00000515425.6	TSL:1 MANE Select	c.46G>C	p.Gly16Arg	missense	Exon 1 of 17	ENSP00000423660.1
	SH3TC2	ENST00000512049.5	TSL:1	c.46G>C	p.Gly16Arg	missense	Exon 1 of 17	ENSP00000421860.1
	SH3TC2	ENST00000323829.9	TSL:1	n.46G>C		non_coding_transcript_exon	Exon 1 of 18	ENSP00000313025.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.046
Eigen_PC	Benign	0.041
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.51
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.29
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.074	T
Polyphen		0.86	P
Vest4		0.21
MutPred		0.14		Loss of ubiquitination at K19 (P = 0.0211)
MVP		0.86
MPC		0.063
ClinPred		0.69	D
GERP RS		3.9
PromoterAI		0.073	Neutral
Varity_R		0.15
gMVP		0.26
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs753975938; hg19: chr5-148442540;