rs35029175

chr3-57912672-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001377540.1(SLMAP):c.1991A>G(p.Gln664Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00113 in 1,612,582 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q664H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: SLMAP NM_001377540.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.26

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]

LOC105377103 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03937456).
• BP6: Variant 3-57912672-A-G is Benign according to our data. Variant chr3-57912672-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 463277.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-57912672-A-G is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 95 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLMAP	NM_001377540.1	c.1991A>G	p.Gln664Arg	missense_variant	20/25	ENST00000671191.1
LOC105377103	XR_007095927.1	n.364+4512T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLMAP	ENST00000671191.1	c.1991A>G	p.Gln664Arg	missense_variant	20/25		NM_001377540.1	P4

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152248 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000549 AC: 137 AN: 249686 Hom.: 0 AF XY: 0.000547 AC XY: 74 AN XY: 135260

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00114

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.00118 AC: 1729 AN: 1460216 Hom.: 2 Cov.: 31 AF XY: 0.00109 AC XY: 789 AN XY: 726114

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00152

Gnomad4 OTH exome AF: 0.000481

GnomAD4 genome AF: 0.000623 AC: 95 AN: 152366 Hom.: 0 Cov.: 32 AF XY: 0.000483 AC XY: 36 AN XY: 74516

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00128

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00104 Hom.: 0

Bravo AF: 0.000552

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000404 AC: 49

EpiCase AF: 0.000763

EpiControl AF: 0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brugada syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.11
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.039	T;T;T;T;T;T
MetaSVM	Benign	-0.47	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0080	D;D;D;D;T;D
Sift4G	Benign	0.56	T;T;T;T;T;T
Polyphen		1.0	D;D;D;D;.;D
Vest4		0.26
MVP		0.57
MPC		0.39
ClinPred		0.026	T
GERP RS		5.3
Varity_R		0.31
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs35029175; hg19: chr3-57898399; COSMIC: COSV99908672; COSMIC: COSV99908672;