19-53992678-A-T

Variant names:

• chr19-53992678-A-T
• rs3810244
• NM_145814.2:c.-200A>T

Variant summary

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

The NM_145814.2(CACNG6):​c.-200A>T variant causes a 5 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: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CACNG6 NM_145814.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 18 publications found

Genes affected

CACNG6 (HGNC:13625): (calcium voltage-gated channel auxiliary subunit gamma 6) Voltage-dependent calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma, and is one of two known gamma subunit proteins. This particular gamma subunit is an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members that function as transmembrane AMPA receptor regulatory proteins (TARPs). Alternative splicing results in multiple transcript variants. Variants in this gene have been associated with aspirin-intolerant asthma. [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=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNG6	NM_145814.2	c.-200A>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000252729.7	NP_665813.1
CACNG6	NM_145815.2	c.-200A>T		5_prime_UTR_variant	Exon 1 of 3		NP_665814.1
CACNG6	NM_031897.3	c.-200A>T		5_prime_UTR_variant	Exon 1 of 2		NP_114103.2
CACNG6	NR_102308.2	n.49+1481A>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNG6	ENST00000252729.7	c.-200A>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_145814.2	ENSP00000252729.2
CACNG6	ENST00000352529.1	c.-200A>T		5_prime_UTR_variant	Exon 1 of 2	5		ENSP00000319135.1
CACNG6	ENST00000346968.2	c.-200A>T		upstream_gene_variant		5		ENSP00000319097.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 222588 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 113182

African (AFR) AF: 0.00 AC: 0 AN: 6098

American (AMR) AF: 0.00 AC: 0 AN: 6398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7886

East Asian (EAS) AF: 0.00 AC: 0 AN: 20322

South Asian (SAS) AF: 0.00 AC: 0 AN: 2294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 144158

Other (OTH) AF: 0.00 AC: 0 AN: 14458

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 117664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.36
PhyloP100		-0.28
PromoterAI		0.0026	Neutral

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: rs3810244; hg19: chr19-54495932;