12-48768815-G-A

Variant names:

• chr12-48768815-G-A
• rs7300155
• NM_015270.5:c.3382-99C>T

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.72
• Publications: 5 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=-0.92).
• 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ADCY6	NM_015270.5	c.3382-99C>T		intron_variant	Intron 21 of 21	ENST00000357869.8	NP_056085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY6	ENST00000357869.8	c.3382-99C>T		intron_variant	Intron 21 of 21	2	NM_015270.5	ENSP00000350536.4
ADCY6	ENST00000307885.4	c.3382-99C>T		intron_variant	Intron 20 of 20	1		ENSP00000311405.4
ADCY6	ENST00000550422.5	c.3223-99C>T		intron_variant	Intron 20 of 20	2		ENSP00000446730.1
ADCY6	ENST00000547260.5	n.2236-99C>T		intron_variant	Intron 6 of 6	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

African (AFR) AF: 0.465 AC: 15002 AN: 32278

American (AMR) AF: 0.0806 AC: 3296 AN: 40870

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3332 AN: 22382

East Asian (EAS) AF: 0.0155 AC: 606 AN: 39116

South Asian (SAS) AF: 0.0940 AC: 7237 AN: 76984

European-Finnish (FIN) AF: 0.0926 AC: 4722 AN: 50998

Middle Eastern (MID) AF: 0.107 AC: 546 AN: 5096

European-Non Finnish (NFE) AF: 0.150 AC: 161830 AN: 1076924

Other (OTH) AF: 0.157 AC: 9093 AN: 57840

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

African (AFR) AF: 0.459 AC: 19002 AN: 41424

American (AMR) AF: 0.131 AC: 2003 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3468

East Asian (EAS) AF: 0.0257 AC: 133 AN: 5178

South Asian (SAS) AF: 0.0951 AC: 459 AN: 4824

European-Finnish (FIN) AF: 0.0922 AC: 977 AN: 10598

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10014 AN: 67968

Other (OTH) AF: 0.182 AC: 383 AN: 2106

Alfa AF: 0.155 Hom.: 1840

Bravo AF: 0.233

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 08, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0050
DANN	Benign	0.54
PhyloP100		-4.7
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: rs7300155; hg19: chr12-49162598;