3-57860714-A-T

Variant names:

• chr3-57860714-A-T
• rs774215191
• NM_001377540.1:c.703A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001377540.1(SLMAP):​c.703A>T​(p.Ser235Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000192 in 1,564,232 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. S235G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLMAP NM_001377540.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.67
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15676326).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377540.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	NM_001377540.1	MANE Select	c.703A>T	p.Ser235Cys	missense	Exon 9 of 25	NP_001364469.1
	SLMAP	NM_001377538.1		c.703A>T	p.Ser235Cys	missense	Exon 9 of 24	NP_001364467.1
	SLMAP	NM_001377539.1		c.703A>T	p.Ser235Cys	missense	Exon 9 of 24	NP_001364468.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.703A>T	p.Ser235Cys	missense	Exon 9 of 25	ENSP00000499458.1
	SLMAP	ENST00000417128.7	TSL:1	c.703A>T	p.Ser235Cys	missense	Exon 9 of 23	ENSP00000412829.3
	SLMAP	ENST00000449503.6	TSL:1	c.703A>T	p.Ser235Cys	missense	Exon 8 of 20	ENSP00000412945.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1412052 Hom.: 0 Cov.: 29 AF XY: 0.00000142 AC XY: 1 AN XY: 701794

African (AFR) AF: 0.00 AC: 0 AN: 30476

American (AMR) AF: 0.00 AC: 0 AN: 31860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24490

East Asian (EAS) AF: 0.00 AC: 0 AN: 38032

South Asian (SAS) AF: 0.00 AC: 0 AN: 76440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5356

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1094438

Other (OTH) AF: 0.00 AC: 0 AN: 58274

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152180 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.77	N
PhyloP100		4.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.18
Sift	Benign	0.030	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.25		Gain of catalytic residue at L236 (P = 0.0107)
MVP		0.33
MPC		0.19
ClinPred		0.64	D
GERP RS		2.9
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.18
Mutation Taster		=254/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs774215191; hg19: chr3-57846441;