rs1553495271

Variant names:

• chr2-166303300-GG-AT
• rs1553495271
• NM_001365536.1:c.690_691delCCinsAT

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP6_Moderate BP7

The NM_001365536.1(SCN9A):​c.690_691delCCinsAT​(p.232) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN9A NM_001365536.1 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

SCN9A (HGNC:10597): (sodium voltage-gated channel alpha subunit 9) This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

ACMG classification

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

• BP6: Variant 2-166303300-GG-AT is Benign according to our data. Variant chr2-166303300-GG-AT is described in ClinVar as Likely_benign. ClinVar VariationId is 471162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.690_691delCCinsAT	p.232	splice_region_variant, synonymous_variant		ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.690_691delCCinsAT	p.232	splice_region_variant, synonymous_variant			NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.690_691delCCinsAT	p.232	splice_region_variant, synonymous_variant		5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.690_691delCCinsAT	p.232	splice_region_variant, synonymous_variant		5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.690_691delCCinsAT	p.232	splice_region_variant, synonymous_variant				ENSP00000495983.1
SCN9A	ENST00000454569.6	c.690_691delCCinsAT	p.232	splice_region_variant, synonymous_variant		1		ENSP00000413212.2
SCN9A	ENST00000452182.2	c.690_691delCCinsAT	p.232	splice_region_variant, synonymous_variant		1		ENSP00000393141.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1

May 03, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553495271; hg19: chr2-167159810;