8-72063566-T-G

Position:

• chr8-72063566-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007332.3(TRPA1):​c.558A>C​(p.Lys186Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,608,096 control chromosomes in the GnomAD database, including 342,578 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.72 (41483 hom., cov: 31)
  • Exomes 𝑓: 0.64 (301095 hom.)
• Consequence: TRPA1 NM_007332.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.535

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]

MSC-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.347031E-7).
• BP6: Variant 8-72063566-T-G is Benign according to our data. Variant chr8-72063566-T-G is described in ClinVar as [Benign]. Clinvar id is 1342284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109810 AN: 151974 Hom.: 41431 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.709

GnomAD3 exomes AF: 0.705 AC: 176918 AN: 251112 Hom.: 64465 AF XY: 0.693 AC XY: 94136 AN XY: 135744

Gnomad AFR exome AF: 0.919

Gnomad AMR exome AF: 0.816

Gnomad ASJ exome AF: 0.678

Gnomad EAS exome AF: 0.990

Gnomad SAS exome AF: 0.737

Gnomad FIN exome AF: 0.630

Gnomad NFE exome AF: 0.604

Gnomad OTH exome AF: 0.651

GnomAD4 exome AF: 0.636 AC: 926101 AN: 1456004 Hom.: 301095 Cov.: 31 AF XY: 0.637 AC XY: 461292 AN XY: 724616

Gnomad4 AFR exome AF: 0.923

Gnomad4 AMR exome AF: 0.806

Gnomad4 ASJ exome AF: 0.680

Gnomad4 EAS exome AF: 0.982

Gnomad4 SAS exome AF: 0.737

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.662

GnomAD4 genome AF: 0.723 AC: 109922 AN: 152092 Hom.: 41483 Cov.: 31 AF XY: 0.725 AC XY: 53908 AN XY: 74336

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.978

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.615

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.709

Alfa AF: 0.642 Hom.: 48051

Bravo AF: 0.742

TwinsUK AF: 0.598 AC: 2217

ALSPAC AF: 0.595 AC: 2295

ESP6500AA AF: 0.917 AC: 4042

ESP6500EA AF: 0.602 AC: 5176

ExAC AF: 0.703 AC: 85357

Asia WGS AF: 0.838 AC: 2913 AN: 3476

EpiCase AF: 0.590

EpiControl AF: 0.589

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Familial episodic pain syndrome with predominantly upper body involvement Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.9
DANN	Benign	0.78
DEOGEN2	Benign	0.061	.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.042	T;T
MetaRNN	Benign	7.3e-7	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.17	.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.11	N;N
REVEL	Benign	0.064
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);
MPC		0.077
ClinPred		0.021	T
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

Other links and lift over

dbSNP: rs7819749; hg19: chr8-72975801;