GeneBe

NM_021098.3:c.819C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_021098.3(CACNA1H):​c.819C>A​(p.Thr273Thr) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. T273T) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CACNA1H
NM_021098.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.34

Publications

1 publications found
Variant links:
Genes affected
CACNA1H (HGNC:1395): (calcium voltage-gated channel subunit alpha1 H) This gene encodes a T-type member of the alpha-1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. The alpha-1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here. Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE). [provided by RefSeq, Jul 2008]
CACNA1H Gene-Disease associations (from GenCC):
  • hyperaldosteronism, familial, type IV
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • childhood absence epilepsy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • epilepsy, childhood absence, susceptibility to, 6
    Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP7
Synonymous conserved (PhyloP=2.34 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1HNM_021098.3 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 35 ENST00000348261.11 NP_066921.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1HENST00000348261.11 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 35 1 NM_021098.3 ENSP00000334198.7
CACNA1HENST00000569107.6 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 34 1 ENSP00000454990.2
CACNA1HENST00000711493.1 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 34 ENSP00000518778.1
CACNA1HENST00000565831.7 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 34 1 ENSP00000455840.1
CACNA1HENST00000711450.1 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 35 ENSP00000518762.1
CACNA1HENST00000564231.6 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 35 1 ENSP00000457555.2
CACNA1HENST00000638323.1 linkc.780C>A p.Thr260Thr synonymous_variant Exon 7 of 35 5 ENSP00000492267.1
CACNA1HENST00000562079.6 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 34 1 ENSP00000454581.2
CACNA1HENST00000711438.1 linkc.780C>A p.Thr260Thr synonymous_variant Exon 7 of 34 ENSP00000518754.1
CACNA1HENST00000711482.1 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 36 ENSP00000518771.1
CACNA1HENST00000711485.1 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 35 ENSP00000518774.1
CACNA1HENST00000711455.1 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 36 ENSP00000518768.1
CACNA1HENST00000711483.1 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 35 ENSP00000518772.1
CACNA1HENST00000711456.1 linkc.819C>A p.Thr273Thr synonymous_variant Exon 7 of 34 ENSP00000518769.1
CACNA1HENST00000621827.2 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 37 6 ENSP00000518766.1
CACNA1HENST00000637236.3 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 34 5 ENSP00000492650.2
CACNA1HENST00000639478.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 35 5 ENSP00000491945.1
CACNA1HENST00000640028.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 35 5 ENSP00000491488.1
CACNA1HENST00000711442.1 linkn.*266C>A non_coding_transcript_exon_variant Exon 6 of 34 ENSP00000518758.1
CACNA1HENST00000711448.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518760.1
CACNA1HENST00000711449.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 35 ENSP00000518761.1
CACNA1HENST00000711451.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518763.1
CACNA1HENST00000711452.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518764.1
CACNA1HENST00000711453.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518765.1
CACNA1HENST00000711484.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 35 ENSP00000518773.1
CACNA1HENST00000711486.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 37 ENSP00000518775.1
CACNA1HENST00000711487.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 36 ENSP00000518776.1
CACNA1HENST00000711488.1 linkn.819C>A non_coding_transcript_exon_variant Exon 7 of 35 ENSP00000518777.1
CACNA1HENST00000711442.1 linkn.*266C>A 3_prime_UTR_variant Exon 6 of 34 ENSP00000518758.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1448124
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
718580
African (AFR)
AF:
0.00
AC:
0
AN:
33094
American (AMR)
AF:
0.00
AC:
0
AN:
43332
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25706
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39304
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84416
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51522
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5724
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1105198
Other (OTH)
AF:
0.00
AC:
0
AN:
59828
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
8.1
DANN
Benign
0.70
PhyloP100
2.3

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

Publications

Other links and lift over

dbSNP: rs72552033; hg19: chr16-1250271; API