chr5-136226102-G-T

Variant names:

• chr5-136226102-G-T
• rs751702897
• NM_020389.3:c.2194C>A

Variant summary

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

The NM_020389.3(TRPC7):​c.2194C>A​(p.Leu732Ile) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L732F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPC7 NM_020389.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.84
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3257946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC7	NM_020389.3	c.2194C>A	p.Leu732Ile	missense_variant	Exon 9 of 12	ENST00000513104.6	NP_065122.1
TRPC7	NM_001376901.1	c.2029C>A	p.Leu677Ile	missense_variant	Exon 8 of 11		NP_001363830.1
TRPC7	NM_001167577.2	c.2011C>A	p.Leu671Ile	missense_variant	Exon 8 of 11		NP_001161049.1
TRPC7	NM_001167576.2	c.1846C>A	p.Leu616Ile	missense_variant	Exon 7 of 10		NP_001161048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC7	ENST00000513104.6	c.2194C>A	p.Leu732Ile	missense_variant	Exon 9 of 12	5	NM_020389.3	ENSP00000426070.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T;.;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L;.;.;.
PhyloP100		3.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.77	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.090	T;T;D;T
Polyphen		0.15	B;.;B;.
Vest4		0.36
MutPred		0.42		Loss of helix (P = 0.0444);.;.;.;
MVP		0.91
MPC		0.70
ClinPred		0.70	D
GERP RS		5.0
Varity_R		0.18
gMVP		0.21
Mutation Taster		=80/20	polymorphism

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

dbSNP: rs751702897; hg19: chr5-135561790;