chr12-48771042-T-C

Variant names:

• chr12-48771042-T-C
• rs9804777
• NM_015270.5:c.3052-72A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015270.5(ADCY6):​c.3052-72A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,476,018 control chromosomes in the GnomAD database, including 15,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1703 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13720 hom.)
• Consequence: ADCY6 NM_015270.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.26
• Publications: 4 publications found

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]

SPMIP11 (HGNC:48628): (sperm microtubule inner protein 11)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-48771042-T-C is Benign according to our data. Variant chr12-48771042-T-C is described in ClinVar as Benign. ClinVar VariationId is 1283688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY6	NM_015270.5	c.3052-72A>G		intron_variant	Intron 19 of 21	ENST00000357869.8	NP_056085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY6	ENST00000357869.8	c.3052-72A>G		intron_variant	Intron 19 of 21	2	NM_015270.5	ENSP00000350536.4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22121 AN: 152042 Hom.: 1701 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0974

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0255

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.0928

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.141 AC: 186046 AN: 1323858 Hom.: 13720 Cov.: 20 AF XY: 0.139 AC XY: 91207 AN XY: 655406

African (AFR) AF: 0.193 AC: 5911 AN: 30644

American (AMR) AF: 0.0689 AC: 2588 AN: 37560

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 3517 AN: 23962

East Asian (EAS) AF: 0.0151 AC: 559 AN: 37032

South Asian (SAS) AF: 0.0985 AC: 7674 AN: 77894

European-Finnish (FIN) AF: 0.0946 AC: 4261 AN: 45038

Middle Eastern (MID) AF: 0.0976 AC: 502 AN: 5146

European-Non Finnish (NFE) AF: 0.152 AC: 153278 AN: 1011170

Other (OTH) AF: 0.140 AC: 7756 AN: 55412

GnomAD4 genome AF: 0.145 AC: 22129 AN: 152160 Hom.: 1703 Cov.: 32 AF XY: 0.140 AC XY: 10401 AN XY: 74402

African (AFR) AF: 0.195 AC: 8081 AN: 41496

American (AMR) AF: 0.0972 AC: 1485 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 491 AN: 3470

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5174

South Asian (SAS) AF: 0.0977 AC: 471 AN: 4820

European-Finnish (FIN) AF: 0.0928 AC: 984 AN: 10602

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.147 AC: 10023 AN: 67998

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.155 Hom.: 548

Bravo AF: 0.147

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.67
DANN	Benign	0.68
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs9804777; hg19: chr12-49164825;