rs199888777

Variant names:

• chr4-121899594-C-T
• rs199888777
• NM_001130698.2:c.2547+18G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-121899594-C-T
• chr4-121899594-C-A
• chr4-121899594-C-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001130698.2(TRPC3):​c.2547+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000513 in 1,599,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (1 hom.)
• Consequence: TRPC3 NM_001130698.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.407
• Publications: 0 publications found

Genes affected

TRPC3 (HGNC:12335): (transient receptor potential cation channel subfamily C member 3) The protein encoded by this gene is a membrane protein that can form a non-selective channel permeable to calcium and other cations. The encoded protein appears to be induced to form channels by a receptor tyrosine kinase-activated phosphatidylinositol second messenger system and also by depletion of intracellular calcium stores. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

TRPC3 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 41

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-121899594-C-T is Benign according to our data. Variant chr4-121899594-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1935051.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130698.2. 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
	TRPC3	NM_001130698.2	MANE Select	c.2547+18G>A		intron	N/A	NP_001124170.1	Q13507-2
	TRPC3	NM_001366479.2		c.2463+3258G>A		intron	N/A	NP_001353408.1
	TRPC3	NM_003305.2		c.2328+18G>A		intron	N/A	NP_003296.1	Q13507-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC3	ENST00000379645.8	TSL:1 MANE Select	c.2547+18G>A		intron	N/A	ENSP00000368966.3	Q13507-2
	TRPC3	ENST00000264811.9	TSL:1	c.2328+18G>A		intron	N/A	ENSP00000264811.5	Q13507-3
	TRPC3	ENST00000513531.1	TSL:1	c.2163+18G>A		intron	N/A	ENSP00000426899.1	J3QTB0

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 151954 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000803 AC: 20 AN: 249220 AF XY: 0.000126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000713

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000525 AC: 76 AN: 1447554 Hom.: 1 Cov.: 28 AF XY: 0.0000763 AC XY: 55 AN XY: 721076

African (AFR) AF: 0.00 AC: 0 AN: 33094

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39496

South Asian (SAS) AF: 0.000431 AC: 37 AN: 85888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.0000309 AC: 34 AN: 1099562

Other (OTH) AF: 0.0000668 AC: 4 AN: 59878

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41502

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000832 AC: 4 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67952

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000189

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.022
DANN	Benign	0.73
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs199888777; hg19: chr4-122820749;