12-48771622-C-T

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.3051+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,585,984 control chromosomes in the GnomAD database, including 2,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (1337 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (1237 hom.)
• Consequence: ADCY6 NM_015270.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.75

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-48771622-C-T is Benign according to our data. Variant chr12-48771622-C-T is described in ClinVar as [Benign]. Clinvar id is 1271510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY6	NM_015270.5	c.3051+88G>A		intron_variant		ENST00000357869.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY6	ENST00000357869.8	c.3051+88G>A		intron_variant		2	NM_015270.5	P1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11045 AN: 152030 Hom.: 1333 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.0574

GnomAD3 exomes AF: 0.0206 AC: 4929 AN: 239488 Hom.: 575 AF XY: 0.0146 AC XY: 1904 AN XY: 130238

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.0139

Gnomad ASJ exome AF: 0.00533

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000426

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000930

Gnomad OTH exome AF: 0.00846

GnomAD4 exome AF: 0.00786 AC: 11267 AN: 1433836 Hom.: 1237 Cov.: 28 AF XY: 0.00674 AC XY: 4818 AN XY: 714688

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.00507

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000598

Gnomad4 FIN exome AF: 0.0000231

Gnomad4 NFE exome AF: 0.000576

Gnomad4 OTH exome AF: 0.0184

GnomAD4 genome AF: 0.0728 AC: 11073 AN: 152148 Hom.: 1337 Cov.: 32 AF XY: 0.0703 AC XY: 5226 AN XY: 74382

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.0317

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0486 Hom.: 153

Bravo AF: 0.0828

Asia WGS AF: 0.0170 AC: 59 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 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.82
Dann	Benign	0.41

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: rs3729972; hg19: chr12-49165405; COSMIC: COSV57166904; COSMIC: COSV57166904;