chr5-136315608-C-T

Variant names:

• chr5-136315608-C-T
• NM_020389.3:c.952G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020389.3(TRPC7):​c.952G>A​(p.Glu318Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPC7 NM_020389.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

TRPC7 (HGNC:20754): (transient receptor potential cation channel subfamily C member 7) Predicted to enable inositol 1,4,5 trisphosphate binding activity and store-operated calcium channel activity. Predicted to be involved in metal ion transport; regulation of cytosolic calcium ion concentration; and single fertilization. Predicted to act upstream of or within calcium ion transport. Predicted to be located in plasma membrane. Predicted to be part of cation channel complex. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRPC7-AS2 (HGNC:40937): (TRPC7 antisense RNA 2)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020389.3. 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
	TRPC7	NM_020389.3	MANE Select	c.952G>A	p.Glu318Lys	missense	Exon 3 of 12	NP_065122.1	Q9HCX4-1
	TRPC7	NM_001376901.1		c.952G>A	p.Glu318Lys	missense	Exon 3 of 11	NP_001363830.1	Q70T25
	TRPC7	NM_001167577.2		c.781-40771G>A		intron	N/A	NP_001161049.1	Q9HCX4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC7	ENST00000513104.6	TSL:5 MANE Select	c.952G>A	p.Glu318Lys	missense	Exon 3 of 12	ENSP00000426070.2	Q9HCX4-1
	TRPC7	ENST00000502753.4	TSL:5	c.952G>A	p.Glu318Lys	missense	Exon 3 of 11	ENSP00000424854.3	Q70T25
	TRPC7	ENST00000378459.7	TSL:5	c.781-40771G>A		intron	N/A	ENSP00000367720.3	Q9HCX4-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.46	N
PhyloP100		7.9
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.33
Sift	Benign	0.045	D
Polyphen		0.010	B
Vest4		0.86
MutPred		0.39		Gain of MoRF binding (P = 0.0073)
MVP		0.71
MPC		0.96
ClinPred		0.80	D
GERP RS		5.6
Varity_R		0.26
gMVP		0.75
Mutation Taster		=16/84	disease causing

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

Other links and lift over

hg19: chr5-135651296; COSMIC: COSV104661835;