NM_020389.3:c.2357G>A

Variant names:

• chr5-136216262-C-T
• rs768651273
• NM_020389.3:c.2357G>A

Variant summary

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

The NM_020389.3(TRPC7):​c.2357G>A​(p.Arg786Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,612,748 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: TRPC7 NM_020389.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82
• 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-AS1 (HGNC:40936): (TRPC7 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

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.2357G>A	p.Arg786Gln	missense	Exon 11 of 12	NP_065122.1	Q9HCX4-1
	TRPC7	NM_001376901.1		c.2192G>A	p.Arg731Gln	missense	Exon 10 of 11	NP_001363830.1	Q70T25
	TRPC7	NM_001167577.2		c.2174G>A	p.Arg725Gln	missense	Exon 10 of 11	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.2357G>A	p.Arg786Gln	missense	Exon 11 of 12	ENSP00000426070.2	Q9HCX4-1
	TRPC7	ENST00000502753.4	TSL:5	c.2192G>A	p.Arg731Gln	missense	Exon 10 of 11	ENSP00000424854.3	Q70T25
	TRPC7	ENST00000378459.7	TSL:5	c.2174G>A	p.Arg725Gln	missense	Exon 10 of 11	ENSP00000367720.3	Q9HCX4-3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246556 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1460576 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 726374

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000466 AC: 4 AN: 85860

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111434

Other (OTH) AF: 0.0000331 AC: 2 AN: 60344

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152172 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000162 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000827 AC: 1

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	0.63
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.41		Gain of methylation at K782 (P = 0.1106)
MVP		0.93
MPC		1.7
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.61
gMVP		0.57
Mutation Taster		=39/61	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs768651273; hg19: chr5-135551950;