rs203849

chr1-167880176-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018417.6(ADCY10):c.1155T>C(p.Gly385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,610,082 control chromosomes in the GnomAD database, including 187,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20842 hom., cov: 32)
  • Exomes 𝑓: 0.48 (166937 hom.)
• Consequence: ADCY10 NM_018417.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.909

Genes affected

ADCY10 (HGNC:21285): (adenylate cyclase 10) The protein encoded by this gene belongs to a distinct class of adenylyl cyclases that is soluble and insensitive to G protein or forskolin regulation. Activity of this protein is regulated by bicarbonate. Variation at this gene has been observed in patients with absorptive hypercalciuria. Alternatively spliced transcript variants encoding different isoforms have been observed. There is a pseudogene of this gene on chromosome 6. [provided by RefSeq, Jul 2014]

DCAF6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-167880176-A-G is Benign according to our data. Variant chr1-167880176-A-G is described in ClinVar as [Benign]. Clinvar id is 1167837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.909 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.1155T>C	p.Gly385=	synonymous_variant	11/33	ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.1155T>C	p.Gly385=	synonymous_variant	11/33	1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.879T>C	p.Gly293=	synonymous_variant	11/33	1
ADCY10	ENST00000545172.5	c.696T>C	p.Gly232=	synonymous_variant	8/30	2

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78436 AN: 151936 Hom.: 20819 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.500

GnomAD3 exomes AF: 0.473 AC: 117391 AN: 247990 Hom.: 28231 AF XY: 0.472 AC XY: 63202 AN XY: 133826

Gnomad AFR exome AF: 0.633

Gnomad AMR exome AF: 0.478

Gnomad ASJ exome AF: 0.522

Gnomad EAS exome AF: 0.325

Gnomad SAS exome AF: 0.461

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.476 AC: 694420 AN: 1458028 Hom.: 166937 Cov.: 38 AF XY: 0.476 AC XY: 345478 AN XY: 725160

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.478

Gnomad4 ASJ exome AF: 0.524

Gnomad4 EAS exome AF: 0.359

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.454

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.480

GnomAD4 genome AF: 0.516 AC: 78507 AN: 152054 Hom.: 20842 Cov.: 32 AF XY: 0.514 AC XY: 38213 AN XY: 74342

Gnomad4 AFR AF: 0.637

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.499

Alfa AF: 0.485 Hom.: 43827

Bravo AF: 0.522

Asia WGS AF: 0.384 AC: 1336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.4
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs203849; hg19: chr1-167849414; COSMIC: COSV63239261;