chr5-149012661-C-G

Position:

• chr5-149012661-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024577.4(SH3TC2):​c.3127G>C​(p.Ala1043Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SH3TC2 NM_024577.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3TC2	NM_024577.4	c.3127G>C	p.Ala1043Pro	missense_variant	13/17	ENST00000515425.6	NP_078853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3TC2	ENST00000515425.6	c.3127G>C	p.Ala1043Pro	missense_variant	13/17	1	NM_024577.4	ENSP00000423660	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.45
Sift	Benign	0.17	T;T
Sift4G	Uncertain	0.019	D;D
Polyphen		1.0	D;.
Vest4		0.85
MutPred		0.37		Loss of ubiquitination at K1042 (P = 0.0504);.;
MVP		0.94
MPC		0.29
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.62
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-148392224;