chr1-167810771-T-C

Variant names:

• chr1-167810771-T-C
• rs1662151205
• NM_018417.6:c.4625A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018417.6(ADCY10):​c.4625A>G​(p.Glu1542Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 3.79
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• idiopathic inherited hypercalciuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31504798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018417.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	NM_018417.6	MANE Select	c.4625A>G	p.Glu1542Gly	missense	Exon 32 of 33	NP_060887.2	Q96PN6-1
	ADCY10	NM_001297772.2		c.4349A>G	p.Glu1450Gly	missense	Exon 32 of 33	NP_001284701.1	Q96PN6-2
	ADCY10	NM_001167749.3		c.4166A>G	p.Glu1389Gly	missense	Exon 29 of 30	NP_001161221.1	Q96PN6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	ENST00000367851.9	TSL:1 MANE Select	c.4625A>G	p.Glu1542Gly	missense	Exon 32 of 33	ENSP00000356825.4	Q96PN6-1
	ADCY10	ENST00000367848.1	TSL:1	c.4349A>G	p.Glu1450Gly	missense	Exon 32 of 33	ENSP00000356822.1	Q96PN6-2
	ADCY10	ENST00000485964.5	TSL:5	n.*1561A>G		non_coding_transcript_exon	Exon 14 of 15	ENSP00000476402.1	V9GY51

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.083
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.8
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.14
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.015	D
Polyphen		0.80	P
Vest4		0.57
MutPred		0.38		Gain of catalytic residue at E1542 (P = 0.0116)
MVP		0.46
MPC		0.32
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.11
gMVP		0.17
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs1662151205; hg19: chr1-167780008;