5-136213470-C-G

Variant names:

• chr5-136213470-C-G
• rs1755159019
• NM_020389.3:c.2554G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020389.3(TRPC7):​c.2554G>C​(p.Asp852His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPC7 NM_020389.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.82

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21172333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC7	NM_020389.3	c.2554G>C	p.Asp852His	missense_variant	Exon 12 of 12	ENST00000513104.6	NP_065122.1
TRPC7	NM_001376901.1	c.2389G>C	p.Asp797His	missense_variant	Exon 11 of 11		NP_001363830.1
TRPC7	NM_001167577.2	c.2371G>C	p.Asp791His	missense_variant	Exon 11 of 11		NP_001161049.1
TRPC7	NM_001167576.2	c.2206G>C	p.Asp736His	missense_variant	Exon 10 of 10		NP_001161048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC7	ENST00000513104.6	c.2554G>C	p.Asp852His	missense_variant	Exon 12 of 12	5	NM_020389.3	ENSP00000426070.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2554G>C (p.D852H) alteration is located in exon 12 (coding exon 12) of the TRPC7 gene. This alteration results from a G to C substitution at nucleotide position 2554, causing the aspartic acid (D) at amino acid position 852 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;.;T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.016	D;D;D;D
Polyphen		0.0010	B;.;B;.
Vest4		0.24
MutPred		0.34		Gain of MoRF binding (P = 0.0457);.;.;.;
MVP		0.79
MPC		0.74
ClinPred		0.91	D
GERP RS		4.9
Varity_R		0.18
gMVP		0.28

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: rs1755159019; hg19: chr5-135549158;