4-8209749-C-G

Variant names:

• chr4-8209749-C-G
• rs144449036
• NM_018986.5:c.174C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018986.5(SH3TC1):​c.174C>G​(p.Asp58Glu) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH3TC1 NM_018986.5 missense, splice_region
• Scores: Splicing: ADA: 0.00003298
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.88

Genes affected

SH3TC1 (HGNC:26009): (SH3 domain and tetratricopeptide repeats 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06415799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3TC1	NM_018986.5	c.174C>G	p.Asp58Glu	missense_variant, splice_region_variant	Exon 3 of 18	ENST00000245105.8	NP_061859.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3TC1	ENST00000245105.8	c.174C>G	p.Asp58Glu	missense_variant, splice_region_variant	Exon 3 of 18	2	NM_018986.5	ENSP00000245105.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250428 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135598

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.0010
DANN	Benign	0.70
DEOGEN2	Benign	0.0029	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.11
Sift	Benign	0.32	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0020	B;.
Vest4		0.15
MutPred		0.23		Loss of glycosylation at P62 (P = 0.0964);Loss of glycosylation at P62 (P = 0.0964);
MVP		0.29
MPC		0.026
ClinPred		0.10	T
GERP RS		-4.4
Varity_R		0.039
gMVP		0.045

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000033
dbscSNV1_RF	Benign	0.014
SpliceAI score (max)		0.020		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: rs144449036; hg19: chr4-8211476;