rs16859886

chr1-167896633-G-Achr1-167896633-G-Cchr1-167896633-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018417.6(ADCY10):c.701C>T(p.Thr234Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 1,611,658 control chromosomes in the GnomAD database, including 5,435 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. T234T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.095 (824 hom., cov: 31)
  • Exomes 𝑓: 0.075 (4611 hom.)
• Consequence: ADCY10 NM_018417.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 1.51

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016402602).
• BP6: Variant 1-167896633-G-A is Benign according to our data. Variant chr1-167896633-G-A is described in ClinVar as [Benign]. Clinvar id is 1167838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.701C>T	p.Thr234Met	missense_variant	7/33	ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.701C>T	p.Thr234Met	missense_variant	7/33	1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.425C>T	p.Thr142Met	missense_variant	7/33	1
ADCY10	ENST00000545172.5	c.242C>T	p.Thr81Met	missense_variant	4/30	2

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14465 AN: 152054 Hom.: 822 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.0850

GnomAD3 exomes AF: 0.0701 AC: 17620 AN: 251454 Hom.: 788 AF XY: 0.0679 AC XY: 9224 AN XY: 135900

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0566

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0258

Gnomad FIN exome AF: 0.0783

Gnomad NFE exome AF: 0.0797

Gnomad OTH exome AF: 0.0826

GnomAD4 exome AF: 0.0746 AC: 108871 AN: 1459486 Hom.: 4611 Cov.: 31 AF XY: 0.0729 AC XY: 52962 AN XY: 726160

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0590

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0254

Gnomad4 FIN exome AF: 0.0826

Gnomad4 NFE exome AF: 0.0780

Gnomad4 OTH exome AF: 0.0777

GnomAD4 genome AF: 0.0952 AC: 14483 AN: 152172 Hom.: 824 Cov.: 31 AF XY: 0.0934 AC XY: 6946 AN XY: 74390

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0824

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0237

Gnomad4 FIN AF: 0.0728

Gnomad4 NFE AF: 0.0780

Gnomad4 OTH AF: 0.0836

Alfa AF: 0.0788 Hom.: 1160

Bravo AF: 0.0987

TwinsUK AF: 0.0828 AC: 307

ALSPAC AF: 0.0755 AC: 291

ESP6500AA AF: 0.153 AC: 676

ESP6500EA AF: 0.0801 AC: 689

ExAC AF: 0.0719 AC: 8725

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.0859

EpiControl AF: 0.0869

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2019	This variant is associated with the following publications: (PMID: 11932268) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -

Familial idiopathic hypercalciuria Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Apr 01, 2002

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	17
Dann	Benign	0.053
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.48	T;T;T
MetaRNN	Benign	0.0016	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	1.4	N;N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.16
MPC		0.12
ClinPred		0.0048	T
GERP RS		5.3
Varity_R		0.059
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.33		Position offset: -38

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

Publications

LitVar

Other links and lift over

dbSNP: rs16859886; hg19: chr1-167865871; COSMIC: COSV63241833;