3-57849792-A-C

Variant names:

• chr3-57849792-A-C
• NM_001377540.1:c.495A>C
• SLMAP p.Leu165Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001377540.1(SLMAP):​c.495A>C​(p.Leu165Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L165L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLMAP NM_001377540.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• 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, ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=1.86 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	NM_001377540.1	MANE Select	c.495A>C	p.Leu165Leu	synonymous	Exon 6 of 25	NP_001364469.1	A0A590UJK3
	SLMAP	NM_001377538.1		c.495A>C	p.Leu165Leu	synonymous	Exon 6 of 24	NP_001364467.1	A0A994J5K5
	SLMAP	NM_001377539.1		c.495A>C	p.Leu165Leu	synonymous	Exon 6 of 24	NP_001364468.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLMAP	ENST00000671191.1	MANE Select	c.495A>C	p.Leu165Leu	synonymous	Exon 6 of 25	ENSP00000499458.1	A0A590UJK3
	SLMAP	ENST00000417128.7	TSL:1	c.495A>C	p.Leu165Leu	synonymous	Exon 6 of 23	ENSP00000412829.3	H7C3M8
	SLMAP	ENST00000449503.6	TSL:1	c.495A>C	p.Leu165Leu	synonymous	Exon 5 of 20	ENSP00000412945.2	Q14BN4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.2
DANN	Benign	0.80
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-57835519;