Genetic Variant SLMAP:p.Gln801Pro (chr3-57922980-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001377540.1(SLMAP):c.2402A>C(p.Gln801Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. Q801R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLMAP
NM_001377540.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.74

Publications

0 publications found

Variant links:

Genes affected

SLMAP (HGNC:16643): (sarcolemma associated protein) This gene encodes a component of a conserved striatin-interacting phosphatase and kinase complex. Striatin family complexes participate in a variety of cellular processes including signaling, cell cycle control, cell migration, Golgi assembly, and apoptosis. The protein encoded by this gene is a coiled-coil, tail-anchored membrane protein with a single C-terminal transmembrane domain that is posttranslationally inserted into membranes. Mutations in this gene are associated with Brugada syndrome, a cardiac channelopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

SLMAP Gene-Disease associations (from GenCC):

Brugada syndrome
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, Orphanet, ClinGen

SLMAP links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3845308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLMAP	NM_001377540.1 link	c.2402A>C	p.Gln801Pro	missense_variant	Exon 23 of 25	ENST00000671191.1	NP_001364469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLMAP	ENST00000671191.1 link	c.2402A>C	p.Gln801Pro	missense_variant	Exon 23 of 25		NM_001377540.1	ENSP00000499458.1		A0A590UJK3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111926

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.084

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

.;.;T;.;T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

.;D;D;D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.38

T;T;T;T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.0

.;.;M;.;.;.

PhyloP100

4.7

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.1

N;N;N;N;D;N

REVEL

Benign

0.18

Sift

Uncertain

0.021

D;D;D;D;D;D

Sift4G

Uncertain

0.044

D;D;D;T;T;T

Polyphen

1.0

D;D;D;D;.;D

Vest4

0.62

MutPred

0.22

.;.;Gain of catalytic residue at Q784 (P = 0.0032);.;.;.;

MVP

0.34

MPC

0.81

ClinPred

0.94

GERP RS

6.2

Varity_R

0.50

gMVP

0.82

Mutation Taster

=43/57

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over