12-48768815-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015270.5(ADCY6):c.3382-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,554,538 control chromosomes in the GnomAD database, including 22,983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (5433 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17550 hom.)
• Consequence: ADCY6 NM_015270.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.72

Genes affected

ADCY6 (HGNC:237): (adenylate cyclase 6) This gene encodes a member of the adenylyl cyclase family of proteins, which are required for the synthesis of cyclic AMP. All members of this family have an intracellular N-terminus, a tandem repeat of six transmembrane domains separated by a cytoplasmic loop, and a C-terminal cytoplasmic domain. The two cytoplasmic regions bind ATP and form the catalytic core of the protein. Adenylyl cyclases are important effectors of transmembrane signaling pathways and are regulated by the activity of G protein coupled receptor signaling. This protein belongs to a small subclass of adenylyl cyclase proteins that are functionally related and are inhibited by protein kinase A, calcium ions and nitric oxide. A mutation in this gene is associated with arthrogryposis multiplex congenita. [provided by RefSeq, May 2015]

TEX49 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-48768815-G-A is Benign according to our data. Variant chr12-48768815-G-A is described in ClinVar as [Benign]. Clinvar id is 1289350.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY6	NM_015270.5	c.3382-99C>T		intron_variant		ENST00000357869.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY6	ENST00000357869.8	c.3382-99C>T		intron_variant		2	NM_015270.5	P1
ADCY6	ENST00000307885.4	c.3382-99C>T		intron_variant		1		P1
ADCY6	ENST00000550422.5	c.3223-99C>T		intron_variant		2
ADCY6	ENST00000547260.5	n.2236-99C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33653 AN: 151932 Hom.: 5424 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0256

Gnomad SAS AF: 0.0953

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.147 AC: 205664 AN: 1402488 Hom.: 17550 Cov.: 30 AF XY: 0.144 AC XY: 99422 AN XY: 690418

Gnomad4 AFR exome AF: 0.465

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.0155

Gnomad4 SAS exome AF: 0.0940

Gnomad4 FIN exome AF: 0.0926

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.222 AC: 33688 AN: 152050 Hom.: 5433 Cov.: 32 AF XY: 0.213 AC XY: 15858 AN XY: 74330

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.0257

Gnomad4 SAS AF: 0.0951

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.182

Alfa AF: 0.152 Hom.: 1488

Bravo AF: 0.233

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.0050
Dann	Benign	0.54

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

LitVar

Other links and lift over

dbSNP: rs7300155; hg19: chr12-49162598;