5-149028289-G-C

Position:

• chr5-149028289-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024577.4(SH3TC2):​c.1443C>G​(p.Asp481Glu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D481D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH3TC2 NM_024577.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13020134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3TC2	NM_024577.4	c.1443C>G	p.Asp481Glu	missense_variant	11/17	ENST00000515425.6	NP_078853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3TC2	ENST00000515425.6	c.1443C>G	p.Asp481Glu	missense_variant	11/17	1	NM_024577.4	ENSP00000423660	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 80

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	5.2
DANN	Benign	0.22
DEOGEN2	Benign	0.059	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.0025
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	0.59	D;D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.28
Sift	Benign	0.94	T;T
Sift4G	Benign	0.96	T;T
Polyphen		0.0070	B;.
Vest4		0.096
MutPred		0.22		Gain of methylation at K484 (P = 0.0725);.;
MVP		0.82
MPC		0.040
ClinPred		0.095	T
GERP RS		5.1
Varity_R		0.065
gMVP		0.098

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

Other links and lift over

dbSNP: rs146666910; hg19: chr5-148407852;