GeneBe

rs35888674

Variant names:

Variant summary

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

The NM_001365536.1(SCN9A):​c.1975-4_1975-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,278,026 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

SCN9A
NM_001365536.1 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.195

Publications

0 publications found
Variant links:
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)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCN9ANM_001365536.1 linkc.1975-4_1975-3delTT splice_region_variant, intron_variant Intron 12 of 26 ENST00000642356.2 NP_001352465.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCN9AENST00000642356.2 linkc.1975-4_1975-3delTT splice_region_variant, intron_variant Intron 12 of 26 NM_001365536.1 ENSP00000495601.1
SCN9AENST00000303354.11 linkc.1975-4_1975-3delTT splice_region_variant, intron_variant Intron 12 of 26 5 ENSP00000304748.7
SCN9AENST00000409672.5 linkc.1942-4_1942-3delTT splice_region_variant, intron_variant Intron 12 of 26 5 ENSP00000386306.1
SCN9AENST00000645907.1 linkc.1942-4_1942-3delTT splice_region_variant, intron_variant Intron 12 of 26 ENSP00000495983.1
SCN9AENST00000454569.6 linkc.1942-4_1942-3delTT splice_region_variant, intron_variant Intron 12 of 14 1 ENSP00000413212.2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000156
AC:
2
AN:
1278026
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
634304
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
28186
American (AMR)
AF:
0.00
AC:
0
AN:
34336
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21820
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33388
South Asian (SAS)
AF:
0.00
AC:
0
AN:
71202
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45934
Middle Eastern (MID)
AF:
0.000195
AC:
1
AN:
5136
European-Non Finnish (NFE)
AF:
0.00000101
AC:
1
AN:
986050
Other (OTH)
AF:
0.00
AC:
0
AN:
51974
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.20

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

Publications

Other links and lift over

dbSNP: rs35888674; hg19: chr2-167138320; COSMIC: COSV57609805; COSMIC: COSV57609805; API