19-4324572-C-G

Variant names:

• chr19-4324572-C-G
• rs376007006
• NM_001013841.2:c.1073-43G>C

Variant summary

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

The NM_017720.3(STAP2):​c.1168G>C​(p.Gly390Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,397,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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. G390C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: STAP2 NM_017720.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902
• Publications: 0 publications found

Genes affected

STAP2 (HGNC:30430): (signal transducing adaptor family member 2) This gene encodes the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase. The encoded protein possesses domains and several tyrosine phosphorylation sites characteristic of adaptor proteins that mediate the interactions linking proteins involved in signal transduction pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

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=0.06904346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017720.3. 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
	STAP2	NM_001013841.2	MANE Select	c.1073-43G>C		intron	N/A	NP_001013863.1	Q9UGK3-1
	STAP2	NM_017720.3		c.1168G>C	p.Gly390Arg	missense	Exon 12 of 13	NP_060190.2	Q9UGK3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAP2	ENST00000594605.6	TSL:1 MANE Select	c.1073-43G>C		intron	N/A	ENSP00000471052.1	Q9UGK3-1
	STAP2	ENST00000970041.1		c.1300G>C	p.Gly434Arg	missense	Exon 12 of 13	ENSP00000640100.1
	STAP2	ENST00000970043.1		c.1168G>C	p.Gly390Arg	missense	Exon 12 of 13	ENSP00000640102.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1397636 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689442

African (AFR) AF: 0.00 AC: 0 AN: 31726

American (AMR) AF: 0.00 AC: 0 AN: 35812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35984

South Asian (SAS) AF: 0.00 AC: 0 AN: 79196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4498

European-Non Finnish (NFE) AF: 0.00000556 AC: 6 AN: 1078352

Other (OTH) AF: 0.00 AC: 0 AN: 57860

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	0.19
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.83
DANN	Benign	0.63
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.90
PrimateAI	Benign	0.37	T
Sift4G	Pathogenic	0.0010	D
Polyphen		0.11	B
Vest4		0.16
MutPred		0.50		Gain of solvent accessibility (P = 0.019)
MVP		0.072
MPC		0.37
ClinPred		0.032	T
GERP RS		-0.77
gMVP		0.063
Mutation Taster		=98/2	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: rs376007006; hg19: chr19-4324569;