rs145177851

Variant names:

• chr17-39212390-C-A
• rs145177851
• NM_198993.5:c.1138G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-39212390-C-A
• chr17-39212390-C-G
• chr17-39212390-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198993.5(STAC2):​c.1138G>T​(p.Val380Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,454,146 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V380M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STAC2 NM_198993.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAC2	NM_198993.5	c.1138G>T	p.Val380Leu	missense_variant	Exon 11 of 11	ENST00000333461.6	NP_945344.1
STAC2	NM_001351360.2	c.712G>T	p.Val238Leu	missense_variant	Exon 11 of 11		NP_001338289.1
STAC2	XM_017024580.2	c.1153G>T	p.Val385Leu	missense_variant	Exon 11 of 11		XP_016880069.1
STAC2	XM_017024581.2	c.988G>T	p.Val330Leu	missense_variant	Exon 9 of 9		XP_016880070.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAC2	ENST00000333461.6	c.1138G>T	p.Val380Leu	missense_variant	Exon 11 of 11	1	NM_198993.5	ENSP00000327509.5
STAC2	ENST00000584501.1	n.*489G>T		non_coding_transcript_exon_variant	Exon 11 of 11	1		ENSP00000463299.1
STAC2	ENST00000584501.1	n.*489G>T		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000463299.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454146 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722632

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

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: 9.03e-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	0.68
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.99	N
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.65		Loss of sheet (P = 0.0817);
MVP		0.82
MPC		0.13
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.71
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs145177851; hg19: chr17-37368643;