rs145177851

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

Scores

3
11
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.18
Variant links:
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]

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ACMG classification

Classification made for transcript

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
STAC2NM_198993.5 linkc.1138G>T p.Val380Leu missense_variant Exon 11 of 11 ENST00000333461.6 NP_945344.1 Q6ZMT1-1D0IN09
STAC2NM_001351360.2 linkc.712G>T p.Val238Leu missense_variant Exon 11 of 11 NP_001338289.1
STAC2XM_017024580.2 linkc.1153G>T p.Val385Leu missense_variant Exon 11 of 11 XP_016880069.1
STAC2XM_017024581.2 linkc.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
STAC2ENST00000333461.6 linkc.1138G>T p.Val380Leu missense_variant Exon 11 of 11 1 NM_198993.5 ENSP00000327509.5 Q6ZMT1-1
STAC2ENST00000584501.1 linkn.*489G>T non_coding_transcript_exon_variant Exon 11 of 11 1 ENSP00000463299.1 J3QKZ0
STAC2ENST00000584501.1 linkn.*489G>T 3_prime_UTR_variant Exon 11 of 11 1 ENSP00000463299.1 J3QKZ0

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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145177851; hg19: chr17-37368643; API