chr1-167810834-C-T

Position:

• chr1-167810834-C-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.4562G>A​(p.Cys1521Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,614,158 control chromosomes in the GnomAD database, including 353 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (325 hom.)
• Consequence: ADCY10 NM_018417.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.568

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027894378).
• BP6: Variant 1-167810834-C-T is Benign according to our data. Variant chr1-167810834-C-T is described in ClinVar as [Benign]. Clinvar id is 1164408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0997 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.4562G>A	p.Cys1521Tyr	missense_variant	32/33	ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.4562G>A	p.Cys1521Tyr	missense_variant	32/33	1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.4286G>A	p.Cys1429Tyr	missense_variant	32/33	1
ADCY10	ENST00000545172.5	c.4103G>A	p.Cys1368Tyr	missense_variant	29/30	2
ADCY10	ENST00000485964.5	c.*1498G>A		3_prime_UTR_variant, NMD_transcript_variant	14/15	5

Frequencies

GnomAD3 genomes AF: 0.00558 AC: 849 AN: 152160 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00712

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.0168 AC: 4220 AN: 251466 Hom.: 256 AF XY: 0.0130 AC XY: 1762 AN XY: 135902

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00468

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00195

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.00514 AC: 7517 AN: 1461880 Hom.: 325 Cov.: 32 AF XY: 0.00459 AC XY: 3338 AN XY: 727244

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00844

Gnomad4 SAS exome AF: 0.000684

Gnomad4 FIN exome AF: 0.000562

Gnomad4 NFE exome AF: 0.00205

Gnomad4 OTH exome AF: 0.00344

GnomAD4 genome AF: 0.00561 AC: 855 AN: 152278 Hom.: 28 Cov.: 32 AF XY: 0.00564 AC XY: 420 AN XY: 74452

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00713

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00147

Gnomad4 OTH AF: 0.00617

Alfa AF: 0.00251 Hom.: 9

Bravo AF: 0.0112

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00233 AC: 20

ExAC AF: 0.0135 AC: 1638

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	8.6
DANN	Benign	0.95
DEOGEN2	Benign	0.087	.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.74	T;T;T
MetaRNN	Benign	0.0028	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	.;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.094	T;T;T
Polyphen		1.0, 1.0	.;D;D
Vest4		0.62
MPC		0.20
ClinPred		0.031	T
GERP RS		2.5
Varity_R		0.14
gMVP		0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs117021474; hg19: chr1-167780071;