rs3213588

Variant names:

• chr1-167809606-G-A
• rs3213588
• NM_018417.6:c.*72C>T

Variant summary

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

The NM_018417.6(ADCY10):​c.*72C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,538,322 control chromosomes in the GnomAD database, including 140,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20867 hom., cov: 32)
  • Exomes 𝑓: 0.41 (119857 hom.)
• Consequence: ADCY10 NM_018417.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0450
• Publications: 11 publications found

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]

ADCY10 Gene-Disease associations (from GenCC):

• hypercalciuria, absorptive, 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• idiopathic inherited hypercalciuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-167809606-G-A is Benign according to our data. Variant chr1-167809606-G-A is described in CliVar as Benign. Clinvar id is 1250999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.*72C>T		3_prime_UTR_variant	Exon 33 of 33	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.*72C>T		3_prime_UTR_variant	Exon 33 of 33	1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000545172.5	c.*72C>T		3_prime_UTR_variant	Exon 30 of 30	2		ENSP00000441992.1
ADCY10	ENST00000367848.1	c.*72C>T		downstream_gene_variant		1		ENSP00000356822.1
ADCY10	ENST00000485964.5	n.*1841C>T		downstream_gene_variant		5		ENSP00000476402.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75438 AN: 151976 Hom.: 20824 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.408 AC: 566029 AN: 1386228 Hom.: 119857 Cov.: 21 AF XY: 0.407 AC XY: 282317 AN XY: 694168

African (AFR) AF: 0.763 AC: 24428 AN: 31996

American (AMR) AF: 0.331 AC: 14724 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 12043 AN: 25656

East Asian (EAS) AF: 0.176 AC: 6921 AN: 39278

South Asian (SAS) AF: 0.374 AC: 31507 AN: 84192

European-Finnish (FIN) AF: 0.420 AC: 22137 AN: 52764

Middle Eastern (MID) AF: 0.489 AC: 2680 AN: 5476

European-Non Finnish (NFE) AF: 0.409 AC: 427140 AN: 1044592

Other (OTH) AF: 0.423 AC: 24449 AN: 57820

GnomAD4 genome AF: 0.497 AC: 75533 AN: 152094 Hom.: 20867 Cov.: 32 AF XY: 0.492 AC XY: 36555 AN XY: 74348

African (AFR) AF: 0.757 AC: 31405 AN: 41506

American (AMR) AF: 0.401 AC: 6133 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1674 AN: 3468

East Asian (EAS) AF: 0.173 AC: 896 AN: 5178

South Asian (SAS) AF: 0.371 AC: 1783 AN: 4808

European-Finnish (FIN) AF: 0.429 AC: 4534 AN: 10572

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27578 AN: 67970

Other (OTH) AF: 0.484 AC: 1021 AN: 2110

Alfa AF: 0.432 Hom.: 66579

Bravo AF: 0.506

Asia WGS AF: 0.314 AC: 1094 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	-0.86
CADD	Benign	1.7
DANN	Benign	0.39
PhyloP100		0.045
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3213588; hg19: chr1-167778843; COSMIC: COSV63240022; COSMIC: COSV63240022;