rs7819749

chr8-72063566-T-Achr8-72063566-T-Cchr8-72063566-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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 Benignin ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRPA1 NM_007332.3 missense
• Clinical Significance: Not reported in ClinVar
• 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:48724): (MSC antisense RNA 1)

ACMG classification

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	UniProt
TRPA1	NM_007332.3	c.558A>T	p.Lys186Asn	missense_variant	5/27	ENST00000262209.5
TRPA1	XM_011517624.3	c.633A>T	p.Lys211Asn	missense_variant	6/28
TRPA1	XM_011517625.3	c.558A>T	p.Lys186Asn	missense_variant	7/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPA1	ENST00000262209.5	c.558A>T	p.Lys186Asn	missense_variant	5/27	1	NM_007332.3	P1
MSC-AS1	ENST00000518916.5	n.469+10950T>A		intron_variant, non_coding_transcript_variant		3
TRPA1	ENST00000523582.5	c.114A>T	p.Lys38Asn	missense_variant	2/24	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251112 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135744

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: 0 AN: 1458372 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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.: 31

ExAC AF: 0.00000824 AC: 1

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	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.2
Dann	Benign	0.73
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.042	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.25	T
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	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;