chr1-167809830-A-C

Position:

• chr1-167809830-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018417.6(ADCY10):​c.4681T>G​(p.Tyr1561Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADCY10 NM_018417.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.4681T>G	p.Tyr1561Asp	missense_variant	33/33	ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.4681T>G	p.Tyr1561Asp	missense_variant	33/33	1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.4405T>G	p.Tyr1469Asp	missense_variant	33/33	1
ADCY10	ENST00000545172.5	c.4222T>G	p.Tyr1408Asp	missense_variant	30/30	2
ADCY10	ENST00000485964.5	c.*1617T>G		3_prime_UTR_variant, NMD_transcript_variant	15/15	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2022

The c.4681T>G (p.Y1561D) alteration is located in exon 33 (coding exon 32) of the ADCY10 gene. This alteration results from a T to G substitution at nucleotide position 4681, causing the tyrosine (Y) at amino acid position 1561 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	.;T;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	.;M;.
MutationTaster	Benign	0.95	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.68
MutPred		0.33		.;Gain of disorder (P = 0.0141);.;
MVP		0.39
MPC		0.69
ClinPred		0.89	D
GERP RS		4.4
Varity_R		0.23
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-167779067;