dbSNP rs1431713676: ADCY10:p.Ile1584Thr (chr1-167809760-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018417.6(ADCY10):c.4751T>C(p.Ile1584Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1584M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ADCY10
NM_018417.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

Publications

0 publications found

Variant links:

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

ADCY10 links:

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ACMG classification

Classification was made for transcript

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=0.30014575).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADCY10	NM_018417.6	MANE Select	c.4751T>C	p.Ile1584Thr	missense	Exon 33 of 33	NP_060887.2	Q96PN6-1
ADCY10	NM_001297772.2		c.4475T>C	p.Ile1492Thr	missense	Exon 33 of 33	NP_001284701.1	Q96PN6-2
ADCY10	NM_001167749.3		c.4292T>C	p.Ile1431Thr	missense	Exon 30 of 30	NP_001161221.1	Q96PN6-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADCY10	ENST00000367851.9	TSL:1 MANE Select	c.4751T>C	p.Ile1584Thr	missense	Exon 33 of 33	ENSP00000356825.4	Q96PN6-1
ADCY10	ENST00000367848.1	TSL:1	c.4475T>C	p.Ile1492Thr	missense	Exon 33 of 33	ENSP00000356822.1	Q96PN6-2
ADCY10	ENST00000485964.5	TSL:5	n.*1687T>C		non_coding_transcript_exon	Exon 15 of 15	ENSP00000476402.1	V9GY51

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.74

M_CAP

Benign

0.010

MetaRNN

Benign

0.30

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

2.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.3

REVEL

Benign

0.15

Sift

Uncertain

0.018

Sift4G

Uncertain

0.0090

Polyphen

0.79

Vest4

0.47

MutPred

0.33

Loss of helix (P = 0.028)

MVP

0.44

MPC

0.32

ClinPred

0.86

GERP RS

5.5

Varity_R

0.086

gMVP

0.24

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over