chr12-2664915-G-A
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000719.7(CACNA1C):c.4323G>A(p.Thr1441Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,794 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 Likely benign (★★).
Frequency
Consequence
NM_000719.7 synonymous
Scores
Clinical Significance
Conservation
Publications
- Timothy syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
- neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizuresInheritance: AD Classification: STRONG Submitted by: Ambry Genetics
- long QT syndromeInheritance: AD Classification: MODERATE Submitted by: ClinGen
- long QT syndrome 8Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- Brugada syndromeInheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: Orphanet, ClinGen
- Brugada syndrome 3Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- intellectual disabilityInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- short QT syndromeInheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen
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ACMG classification
Our verdict: Benign. The variant received -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1C | NM_000719.7 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | ENST00000399655.6 | NP_000710.5 | |
CACNA1C | NM_001167623.2 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | ENST00000399603.6 | NP_001161095.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1C | ENST00000399603.6 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | 5 | NM_001167623.2 | ENSP00000382512.1 | ||
CACNA1C | ENST00000399655.6 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | 1 | NM_000719.7 | ENSP00000382563.1 | ||
CACNA1C | ENST00000682544.1 | c.4557G>A | p.Thr1519Thr | synonymous_variant | Exon 37 of 50 | ENSP00000507184.1 | ||||
CACNA1C | ENST00000406454.8 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 48 | 5 | ENSP00000385896.3 | |||
CACNA1C | ENST00000399634.6 | c.4290G>A | p.Thr1430Thr | synonymous_variant | Exon 34 of 47 | 5 | ENSP00000382542.2 | |||
CACNA1C | ENST00000683824.1 | c.4488G>A | p.Thr1496Thr | synonymous_variant | Exon 36 of 48 | ENSP00000507867.1 | ||||
CACNA1C | ENST00000347598.9 | c.4467G>A | p.Thr1489Thr | synonymous_variant | Exon 37 of 49 | 1 | ENSP00000266376.6 | |||
CACNA1C | ENST00000344100.7 | c.4389G>A | p.Thr1463Thr | synonymous_variant | Exon 35 of 47 | 1 | ENSP00000341092.3 | |||
CACNA1C | ENST00000327702.12 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 48 | 1 | ENSP00000329877.7 | |||
CACNA1C | ENST00000399617.6 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 48 | 5 | ENSP00000382526.1 | |||
CACNA1C | ENST00000682462.1 | c.4413G>A | p.Thr1471Thr | synonymous_variant | Exon 35 of 47 | ENSP00000507105.1 | ||||
CACNA1C | ENST00000683781.1 | c.4413G>A | p.Thr1471Thr | synonymous_variant | Exon 35 of 47 | ENSP00000507434.1 | ||||
CACNA1C | ENST00000683840.1 | c.4413G>A | p.Thr1471Thr | synonymous_variant | Exon 35 of 47 | ENSP00000507612.1 | ||||
CACNA1C | ENST00000683956.1 | c.4413G>A | p.Thr1471Thr | synonymous_variant | Exon 35 of 47 | ENSP00000506882.1 | ||||
CACNA1C | ENST00000399638.5 | c.4407G>A | p.Thr1469Thr | synonymous_variant | Exon 36 of 48 | 1 | ENSP00000382547.1 | |||
CACNA1C | ENST00000335762.10 | c.4398G>A | p.Thr1466Thr | synonymous_variant | Exon 36 of 48 | 5 | ENSP00000336982.5 | |||
CACNA1C | ENST00000399606.5 | c.4383G>A | p.Thr1461Thr | synonymous_variant | Exon 36 of 48 | 1 | ENSP00000382515.1 | |||
CACNA1C | ENST00000399621.5 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | 1 | ENSP00000382530.1 | |||
CACNA1C | ENST00000399637.5 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | 1 | ENSP00000382546.1 | |||
CACNA1C | ENST00000402845.7 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | 1 | ENSP00000385724.3 | |||
CACNA1C | ENST00000399629.5 | c.4374G>A | p.Thr1458Thr | synonymous_variant | Exon 35 of 47 | 1 | ENSP00000382537.1 | |||
CACNA1C | ENST00000682336.1 | c.4365G>A | p.Thr1455Thr | synonymous_variant | Exon 35 of 47 | ENSP00000507898.1 | ||||
CACNA1C | ENST00000399591.5 | c.4290G>A | p.Thr1430Thr | synonymous_variant | Exon 34 of 46 | 1 | ENSP00000382500.1 | |||
CACNA1C | ENST00000399595.5 | c.4290G>A | p.Thr1430Thr | synonymous_variant | Exon 34 of 46 | 1 | ENSP00000382504.1 | |||
CACNA1C | ENST00000399649.5 | c.4284G>A | p.Thr1428Thr | synonymous_variant | Exon 34 of 46 | 1 | ENSP00000382557.1 | |||
CACNA1C | ENST00000399597.5 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | 1 | ENSP00000382506.1 | |||
CACNA1C | ENST00000399601.5 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | 1 | ENSP00000382510.1 | |||
CACNA1C | ENST00000399641.6 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | 1 | ENSP00000382549.1 | |||
CACNA1C | ENST00000399644.5 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | 1 | ENSP00000382552.1 | |||
CACNA1C | ENST00000682835.1 | c.4323G>A | p.Thr1441Thr | synonymous_variant | Exon 35 of 47 | ENSP00000507282.1 | ||||
CACNA1C | ENST00000683482.1 | c.4314G>A | p.Thr1438Thr | synonymous_variant | Exon 35 of 47 | ENSP00000507169.1 | ||||
CACNA1C | ENST00000682686.1 | c.4290G>A | p.Thr1430Thr | synonymous_variant | Exon 34 of 46 | ENSP00000507309.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00000801 AC: 2AN: 249634 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461580Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727064 show subpopulations
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74364 show subpopulations
ClinVar
Submissions by phenotype
not provided Benign:1
- -
Long QT syndrome Benign:1
- -
Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at