Genetic Variant NM_001365536.1:c.3056A>C (chr2-166272694-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365536.1(SCN9A):c.3056A>C(p.Lys1019Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,318 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. K1019R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SCN9A
NM_001365536.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0400

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]

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: 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=0.19804847).

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	HGVSp	Effect	Exon Rank	Protein
SCN9A	NM_001365536.1	MANE Select	c.3056A>C	p.Lys1019Thr	missense	Exon 17 of 27	NP_001352465.1
SCN9A	NM_002977.4		c.3023A>C	p.Lys1008Thr	missense	Exon 17 of 27	NP_002968.2
SCN1A-AS1	NR_110260.1		n.870-4394T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SCN9A	ENST00000642356.2	MANE Select	c.3056A>C	p.Lys1019Thr	missense	Exon 17 of 27	ENSP00000495601.1
SCN9A	ENST00000303354.11	TSL:5	c.3056A>C	p.Lys1019Thr	missense	Exon 17 of 27	ENSP00000304748.7
SCN9A	ENST00000409672.5	TSL:5	c.3023A>C	p.Lys1008Thr	missense	Exon 17 of 27	ENSP00000386306.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446318

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717688

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32580

American (AMR)

AF:

0.00

AC:

AN:

42104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25550

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

83494

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53062

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104760

Other (OTH)

AF:

0.00

AC:

AN:

59630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

Eigen

Benign

-0.098

Eigen_PC

Benign

-0.052

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.20

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.6

PhyloP100

0.040

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.39

Sift

Uncertain

0.0010

Sift4G

Benign

0.14

Vest4

0.19

MutPred

0.46

Loss of MoRF binding (P = 0.0295)

MVP

0.64

MPC

0.26

ClinPred

0.73

GERP RS

5.4

Varity_R

0.34

gMVP

0.31

Mutation Taster

=70/30

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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