11-101583757-G-T

Variant names:

• chr11-101583757-G-T
• rs3824934
• NM_004621.6:c.-254C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004621.6(TRPC6):​c.-254C>A 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: 33)
  • 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: -0.330
• Publications: 18 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC6	NM_004621.6	c.-254C>A		5_prime_UTR_variant	Exon 1 of 13	ENST00000344327.8	NP_004612.2
TRPC6	NM_001439335.1	c.-254C>A		5_prime_UTR_variant	Exon 1 of 11		NP_001426264.1
TRPC6	XM_047427510.1	c.-254C>A		5_prime_UTR_variant	Exon 1 of 11		XP_047283466.1
TRPC6	XM_047427509.1	c.-89+175C>A		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.-254C>A		5_prime_UTR_variant	Exon 1 of 13	1	NM_004621.6	ENSP00000340913.3
TRPC6	ENST00000526713.1	n.266-78959C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 242472 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 123230

African (AFR) AF: 0.00 AC: 0 AN: 6756

American (AMR) AF: 0.00 AC: 0 AN: 7000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8882

East Asian (EAS) AF: 0.00 AC: 0 AN: 21606

South Asian (SAS) AF: 0.00 AC: 0 AN: 4510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 156514

Other (OTH) AF: 0.00 AC: 0 AN: 15800

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.87
PhyloP100		-0.33
PromoterAI		-0.082	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3824934; hg19: chr11-101454488;