3-53813035-G-T

Variant names:

• chr3-53813035-G-T
• rs893363
• NM_000720.4:c.*1629G>T

Variant summary

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

The NM_000720.4(CACNA1D):​c.*1629G>T variant causes a 3 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: 32)
• Consequence: CACNA1D NM_000720.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 21 publications found

Genes affected

CACNA1D (HGNC:1391): (calcium voltage-gated channel subunit alpha1 D) Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

CHDH (HGNC:24288): (choline dehydrogenase) The protein encoded by this gene is a choline dehydrogenase that localizes to the mitochondrion. Variations in this gene can affect susceptibility to choline deficiency. A few transcript variants have been found for this gene, but the full-length nature of only one has been characterized to date. [provided by RefSeq, Dec 2010]

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=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000720.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1D	NM_000720.4	MANE Plus Clinical	c.*1629G>T		3_prime_UTR	Exon 49 of 49	NP_000711.1
	CACNA1D	NM_001128840.3	MANE Select	c.*1629G>T		3_prime_UTR	Exon 48 of 48	NP_001122312.1
	CHDH	NM_018397.5	MANE Select	c.*4742C>A		3_prime_UTR	Exon 9 of 9	NP_060867.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1D	ENST00000288139.11	TSL:1 MANE Plus Clinical	c.*1629G>T		3_prime_UTR	Exon 49 of 49	ENSP00000288139.3
	CACNA1D	ENST00000350061.11	TSL:1 MANE Select	c.*1629G>T		3_prime_UTR	Exon 48 of 48	ENSP00000288133.5
	CHDH	ENST00000315251.11	TSL:1 MANE Select	c.*4742C>A		3_prime_UTR	Exon 9 of 9	ENSP00000319851.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.20
DANN	Benign	0.67
PhyloP100		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs893363; hg19: chr3-53847062;