chr4-8209753-G-A

Variant names:

• chr4-8209753-G-A
• NM_018986.5:c.178G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018986.5(SH3TC1):​c.178G>A​(p.Ala60Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SH3TC1 NM_018986.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.230
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052390605).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018986.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3TC1	NM_018986.5	MANE Select	c.178G>A	p.Ala60Thr	missense	Exon 3 of 18	NP_061859.4
	SH3TC1	NM_001410712.1		c.178G>A	p.Ala60Thr	missense	Exon 3 of 18	NP_001397641.1	A0A804HI81
	SH3TC1	NM_001318480.2		c.-51G>A		5_prime_UTR	Exon 3 of 18	NP_001305409.2	H0YA34

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3TC1	ENST00000245105.8	TSL:2 MANE Select	c.178G>A	p.Ala60Thr	missense	Exon 3 of 18	ENSP00000245105.3	Q8TE82
	SH3TC1	ENST00000502669.5	TSL:1	n.173-2948G>A		intron	N/A	ENSP00000425970.1	D6RI07
	SH3TC1	ENST00000457650.7	TSL:5	c.178G>A	p.Ala60Thr	missense	Exon 4 of 19	ENSP00000390311.3	Q8TE82

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461490 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727036

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53092

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111992

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	3.1
DANN	Benign	0.73
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.23
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.10
Sift	Benign	0.39	T
Sift4G	Benign	0.54	T
Polyphen		0.0020	B
Vest4		0.12
MutPred		0.23		Loss of glycosylation at P62 (P = 0.0964)
MVP		0.34
MPC		0.026
ClinPred		0.026	T
GERP RS		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.080
Mutation Taster		=296/4	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

hg19: chr4-8211480;