NM_007332.3:c.2564A>G

Variant names:

• chr8-72034369-T-C
• rs398123010
• NM_007332.3:c.2564A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_007332.3(TRPA1):​c.2564A>G​(p.Asn855Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPA1 NM_007332.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.47
• Publications: 44 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-72034369-T-C is Pathogenic according to our data. Variant chr8-72034369-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 39602.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.1591335). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007332.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	NM_007332.3	MANE Select	c.2564A>G	p.Asn855Ser	missense	Exon 22 of 27	NP_015628.2	O75762
	MSC-AS1	NR_033651.1		n.434-18170T>C		intron	N/A
	MSC-AS1	NR_033652.1		n.1029-18170T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.2564A>G	p.Asn855Ser	missense	Exon 22 of 27	ENSP00000262209.4	O75762
	MSC-AS1	ENST00000457356.9	TSL:1	n.511-18170T>C		intron	N/A
	TRPA1	ENST00000859810.1		c.2564A>G	p.Asn855Ser	missense	Exon 24 of 29	ENSP00000529869.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Familial episodic pain syndrome with predominantly upper body involvement (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.025
Sift	Benign	0.24	T
Sift4G	Benign	0.48	T
Polyphen		0.097	B
Vest4		0.67
MutPred		0.48		Gain of methylation at R852 (P = 0.3294)
MVP		0.45
MPC		0.21
ClinPred		0.19	T
GERP RS		3.2
Varity_R		0.25
gMVP		0.34
Mutation Taster		=91/9	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs398123010; hg19: chr8-72946604;