Genetic Variant SCN9A:c.901+1314G>T (chr2-166301776-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001365536.1(SCN9A):c.901+1314G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 150,228 control chromosomes in the GnomAD database, including 27,816 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 27816 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

SCN9A
NM_001365536.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.219

Publications

8 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]

SCN9A links:

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

SCN1A-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365536.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN9A	NM_001365536.1	MANE Select	c.901+1314G>T	intron	N/A	NP_001352465.1	Q15858-1
SCN9A	NM_002977.4		c.901+1314G>T	intron	N/A	NP_002968.2	Q15858-3
SCN1A-AS1	NR_110260.1		n.2297C>A	non_coding_transcript_exon	Exon 12 of 12

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN9A	ENST00000642356.2	MANE Select	c.901+1314G>T	intron	N/A	ENSP00000495601.1	Q15858-1
SCN9A	ENST00000303354.11	TSL:5	c.901+1314G>T	intron	N/A	ENSP00000304748.7	Q15858-1
SCN9A	ENST00000409672.5	TSL:5	c.901+1314G>T	intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

89773

AN:

150116

Hom.:

27792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.611

Gnomad SAS

AF:

0.556

Gnomad FIN

AF:

0.621

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.579

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.598

AC:

89837

AN:

150228

Hom.:

27816

Cov.:

AF XY:

0.599

AC XY:

43944

AN XY:

73416

show subpopulations

African (AFR)

AF:

0.665

AC:

26466

AN:

39820

American (AMR)

AF:

0.585

AC:

8912

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

2073

AN:

3470

East Asian (EAS)

AF:

0.611

AC:

3149

AN:

5158

South Asian (SAS)

AF:

0.556

AC:

2678

AN:

4818

European-Finnish (FIN)

AF:

0.621

AC:

6543

AN:

10530

Middle Eastern (MID)

AF:

0.521

AC:

152

AN:

292

European-Non Finnish (NFE)

AF:

0.564

AC:

38290

AN:

67922

Other (OTH)

AF:

0.581

AC:

1214

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1785

3571

5356

7142

8927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.621

Hom.:

7093

Bravo

AF:

0.600

Asia WGS

AF:

0.605

AC:

2080

AN:

3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.9

(source)

DANN

Benign

0.85

PhyloP100

0.22

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over