Variant rs7819749 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007332.3(TRPA1):c.558A>T(p.Lys186Asn) variant causes a missense 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRPA1
NM_007332.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.535

Variant links:

Genes affected

TRPA1 (HGNC:497): (transient receptor potential cation channel subfamily A member 1) The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control. [provided by RefSeq, Jul 2008]

TRPA1 links:

MSC-AS1 (HGNC:):

MSC-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06286767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPA1	NM_007332.3 linkuse as main transcript	c.558A>T	p.Lys186Asn	missense_variant	5/27	ENST00000262209.5	NP_015628.2	O75762
TRPA1	XM_011517624.3 linkuse as main transcript	c.633A>T	p.Lys211Asn	missense_variant	6/28		XP_011515926.1
TRPA1	XM_011517625.3 linkuse as main transcript	c.558A>T	p.Lys186Asn	missense_variant	7/29		XP_011515927.1	O75762

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRPA1	ENST00000262209.5 linkuse as main transcript	c.558A>T	p.Lys186Asn	missense_variant	5/27	1	NM_007332.3	ENSP00000262209.4	O75762
TRPA1	ENST00000523582.5 linkuse as main transcript	c.114A>T	p.Lys38Asn	missense_variant	2/24	5		ENSP00000428151.1	H0YAW0
MSC-AS1	ENST00000518916.5 linkuse as main transcript	n.469+10950T>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251112

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1458372

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725722

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.2

DANN

Benign

0.73

DEOGEN2

Benign

0.061

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.042

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.17

.;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.065

Sift

Benign

0.47

T;T

Sift4G

Benign

0.79

T;T

Polyphen

0.0

.;B

Vest4

0.030

MutPred

0.30

.;Loss of MoRF binding (P = 0.0592);

MVP

0.33

MPC

0.077

ClinPred

0.034

GERP RS

-11

Varity_R

0.043

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over