NM_004621.6:c.*314C>G

Variant names:

• chr11-101452641-G-C
• rs199583740
• NM_004621.6:c.*314C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004621.6(TRPC6):​c.*314C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 301,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: TRPC6 NM_004621.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.342
• Publications: 0 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-101452641-G-C is Benign according to our data. Variant chr11-101452641-G-C is described in ClinVar as Benign. ClinVar VariationId is 301892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000788 (120/152254) while in subpopulation AFR AF = 0.00279 (116/41552). AF 95% confidence interval is 0.00238. There are 0 homozygotes in GnomAd4. There are 56 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 120 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004621.6. 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
	TRPC6	NM_004621.6	MANE Select	c.*314C>G		3_prime_UTR	Exon 13 of 13	NP_004612.2
	TRPC6	NM_001439335.1		c.*314C>G		3_prime_UTR	Exon 11 of 11	NP_001426264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC6	ENST00000344327.8	TSL:1 MANE Select	c.*314C>G		3_prime_UTR	Exon 13 of 13	ENSP00000340913.3	Q9Y210-1
	TRPC6	ENST00000893221.1		c.*314C>G		3_prime_UTR	Exon 13 of 13	ENSP00000563280.1
	TRPC6	ENST00000893220.1		c.*314C>G		3_prime_UTR	Exon 12 of 12	ENSP00000563279.1

Frequencies

GnomAD3 genomes AF: 0.000789 AC: 120 AN: 152136 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.0000938 AC: 14 AN: 149310 Hom.: 0 Cov.: 0 AF XY: 0.0000875 AC XY: 7 AN XY: 79998

African (AFR) AF: 0.00253 AC: 12 AN: 4736

American (AMR) AF: 0.000316 AC: 2 AN: 6320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4142

East Asian (EAS) AF: 0.00 AC: 0 AN: 7860

South Asian (SAS) AF: 0.00 AC: 0 AN: 20622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 90846

Other (OTH) AF: 0.00 AC: 0 AN: 7996

GnomAD4 genome AF: 0.000788 AC: 120 AN: 152254 Hom.: 0 Cov.: 33 AF XY: 0.000752 AC XY: 56 AN XY: 74434

African (AFR) AF: 0.00279 AC: 116 AN: 41552

American (AMR) AF: 0.000131 AC: 2 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000783 Hom.: 0

Bravo AF: 0.000850

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Focal segmental glomerulosclerosis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.40
PhyloP100		-0.34

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: rs199583740; hg19: chr11-101323372;