Genetic Variant ADCY10:p.Leu1572His (chr1-167809796-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018417.6(ADCY10):c.4715T>A(p.Leu1572His) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1572P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ADCY10
NM_018417.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.600

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17980248).

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.4715T>A	p.Leu1572His	missense	Exon 33 of 33	NP_060887.2	Q96PN6-1
ADCY10	NM_001297772.2		c.4439T>A	p.Leu1480His	missense	Exon 33 of 33	NP_001284701.1	Q96PN6-2
ADCY10	NM_001167749.3		c.4256T>A	p.Leu1419His	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.4715T>A	p.Leu1572His	missense	Exon 33 of 33	ENSP00000356825.4	Q96PN6-1
ADCY10	ENST00000367848.1	TSL:1	c.4439T>A	p.Leu1480His	missense	Exon 33 of 33	ENSP00000356822.1	Q96PN6-2
ADCY10	ENST00000485964.5	TSL:5	n.*1651T>A		non_coding_transcript_exon	Exon 15 of 15	ENSP00000476402.1	V9GY51

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251408

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.40

CADD

Benign

8.2

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.22

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.57

M_CAP

Benign

0.010

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

0.60

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.7

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.97

Vest4

0.53

MutPred

0.41

Gain of disorder (P = 0.0339)

MVP

0.26

MPC

0.40

ClinPred

0.44

GERP RS

-1.1

Varity_R

0.13

gMVP

0.37

Mutation Taster

=93/7

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