Genetic Variant NM_018417.6:c.1968T>C (chr1-167856368-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018417.6(ADCY10):c.1968T>C(p.Phe656Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,870 control chromosomes in the GnomAD database, including 18,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1955 hom., cov: 32)

Exomes 𝑓: 0.14 ( 16693 hom. )

Consequence

ADCY10
NM_018417.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.00700

Publications

12 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
idiopathic inherited hypercalciuria
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADCY10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 1-167856368-A-G is Benign according to our data. Variant chr1-167856368-A-G is described in ClinVar as Benign. ClinVar VariationId is 1164409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.007 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

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
ADCY10	NM_018417.6	MANE Select	c.1968T>C	p.Phe656Phe	synonymous	Exon 17 of 33	NP_060887.2
ADCY10	NM_001297772.2		c.1692T>C	p.Phe564Phe	synonymous	Exon 17 of 33	NP_001284701.1
ADCY10	NM_001167749.3		c.1509T>C	p.Phe503Phe	synonymous	Exon 14 of 30	NP_001161221.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADCY10	ENST00000367851.9	TSL:1 MANE Select	c.1968T>C	p.Phe656Phe	synonymous	Exon 17 of 33	ENSP00000356825.4
ADCY10	ENST00000367848.1	TSL:1	c.1692T>C	p.Phe564Phe	synonymous	Exon 17 of 33	ENSP00000356822.1
ADCY10	ENST00000545172.5	TSL:2	c.1509T>C	p.Phe503Phe	synonymous	Exon 14 of 30	ENSP00000441992.1

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

21977

AN:

151988

Hom.:

1944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0972

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.188

AC:

47201

AN:

251390

AF XY:

0.181

show subpopulations

Gnomad AFR exome

AF:

0.0946

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.206

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.135

AC:

197580

AN:

1461764

Hom.:

16693

Cov.:

AF XY:

0.137

AC XY:

99276

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.0983

AC:

3290

AN:

33480

American (AMR)

AF:

0.321

AC:

14369

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3930

AN:

26132

East Asian (EAS)

AF:

0.416

AC:

16526

AN:

39700

South Asian (SAS)

AF:

0.191

AC:

16444

AN:

86254

European-Finnish (FIN)

AF:

0.199

AC:

10617

AN:

53420

Middle Eastern (MID)

AF:

0.221

AC:

1272

AN:

5768

European-Non Finnish (NFE)

AF:

0.110

AC:

122301

AN:

1111896

Other (OTH)

AF:

0.146

AC:

8831

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

9447

18894

28341

37788

47235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4728

9456

14184

18912

23640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.145

AC:

22010

AN:

152106

Hom.:

1955

Cov.:

AF XY:

0.154

AC XY:

11421

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0974

AC:

4043

AN:

41514

American (AMR)

AF:

0.242

AC:

3702

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

537

AN:

3466

East Asian (EAS)

AF:

0.423

AC:

2181

AN:

5156

South Asian (SAS)

AF:

0.207

AC:

996

AN:

4822

European-Finnish (FIN)

AF:

0.209

AC:

2205

AN:

10562

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7732

AN:

67986

Other (OTH)

AF:

0.186

AC:

392

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

949

1898

2847

3796

4745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.132

Hom.:

5482

Bravo

AF:

0.150

Asia WGS

AF:

0.312

AC:

1085

AN:

3478

EpiCase

AF:

0.123

EpiControl

AF:

0.123

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

4.6

(source)

DANN

Benign

0.34

PhyloP100

0.0070

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over