11-101583864-T-G

Variant names:

• chr11-101583864-T-G
• rs41302375
• NM_004621.6:c.-361A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004621.6(TRPC6):​c.-361A>C variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRPC6 NM_004621.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 9 publications found

Genes affected

TRPC6 (HGNC:12338): (transient receptor potential cation channel subfamily C member 6) The protein encoded by this gene forms a receptor-activated calcium channel in the cell membrane. The channel is activated by diacylglycerol and is thought to be under the control of a phosphatidylinositol second messenger system. Activation of this channel occurs independently of protein kinase C and is not triggered by low levels of intracellular calcium. Defects in this gene are a cause of focal segmental glomerulosclerosis 2 (FSGS2). [provided by RefSeq, Mar 2009]

TRPC6 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.-361A>C		5_prime_UTR_variant	Exon 1 of 13	ENST00000344327.8	NP_004612.2
TRPC6	NM_001439335.1	c.-361A>C		5_prime_UTR_variant	Exon 1 of 11		NP_001426264.1
TRPC6	XM_047427510.1	c.-361A>C		5_prime_UTR_variant	Exon 1 of 11		XP_047283466.1
TRPC6	XM_047427509.1	c.-89+68A>C		intron_variant	Intron 1 of 12		XP_047283465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC6	ENST00000344327.8	c.-361A>C		5_prime_UTR_variant	Exon 1 of 13	1	NM_004621.6	ENSP00000340913.3
TRPC6	ENST00000526713.1	n.266-79066A>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 63390 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 31678

African (AFR) AF: 0.00 AC: 0 AN: 2548

American (AMR) AF: 0.00 AC: 0 AN: 1784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2790

East Asian (EAS) AF: 0.00 AC: 0 AN: 4836

South Asian (SAS) AF: 0.00 AC: 0 AN: 802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 376

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 41848

Other (OTH) AF: 0.00 AC: 0 AN: 4476

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		2.1
PromoterAI		-0.015	Neutral

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: rs41302375; hg19: chr11-101454595;