NM_198993.5:c.755A>G

Variant names:

• chr17-39214968-T-C
• rs2046388530
• NM_198993.5:c.755A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_198993.5(STAC2):​c.755A>G​(p.Glu252Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: STAC2 NM_198993.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• Publications: 0 publications found

Genes affected

STAC2 (HGNC:23990): (SH3 and cysteine rich domain 2) This gene encodes a protein containing an SH3 domain and a zinc finger domain. The encoded protein has been shown to regulate calcium channel inactivation in a human cell line. Reduced expression of this gene has been observed in human heart failure. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: -0.099891 (below the threshold of 3.09). Trascript score misZ: 0.30072 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.18659204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198993.5. 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
	STAC2	NM_198993.5	MANE Select	c.755A>G	p.Glu252Gly	missense	Exon 6 of 11	NP_945344.1	Q6ZMT1-1
	STAC2	NM_001351360.2		c.329A>G	p.Glu110Gly	missense	Exon 6 of 11	NP_001338289.1	Q6ZMT1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAC2	ENST00000333461.6	TSL:1 MANE Select	c.755A>G	p.Glu252Gly	missense	Exon 6 of 11	ENSP00000327509.5	Q6ZMT1-1
	STAC2	ENST00000584501.1	TSL:1	n.*106A>G		non_coding_transcript_exon	Exon 6 of 11	ENSP00000463299.1	J3QKZ0
	STAC2	ENST00000584501.1	TSL:1	n.*106A>G		3_prime_UTR	Exon 6 of 11	ENSP00000463299.1	J3QKZ0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.11
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.055
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.27
Sift	Benign	0.060	T
Sift4G	Benign	0.097	T
Polyphen		0.030	B
Vest4		0.39
MutPred		0.21		Loss of stability (P = 0.0786)
MVP		0.79
MPC		0.19
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.39

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: rs2046388530; hg19: chr17-37371221;