1-167810745-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018417.6(ADCY10):c.4651T>C(p.Cys1551Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,614,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: ADCY10 NM_018417.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.522

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01226148).
• BP6: Variant 1-167810745-A-G is Benign according to our data. Variant chr1-167810745-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1078675.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0012 (183/152306) while in subpopulation AFR AF= 0.00402 (167/41568). AF 95% confidence interval is 0.00352. There are 0 homozygotes in gnomad4. There are 78 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 183 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.4651T>C	p.Cys1551Arg	missense_variant	32/33	ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.4651T>C	p.Cys1551Arg	missense_variant	32/33	1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.4375T>C	p.Cys1459Arg	missense_variant	32/33	1
ADCY10	ENST00000545172.5	c.4192T>C	p.Cys1398Arg	missense_variant	29/30	2
ADCY10	ENST00000485964.5	c.*1587T>C		3_prime_UTR_variant, NMD_transcript_variant	14/15	5

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 183 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000414 AC: 104 AN: 251306 Hom.: 0 AF XY: 0.000361 AC XY: 49 AN XY: 135820

Gnomad AFR exome AF: 0.00382

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000153 AC: 224 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.000150 AC XY: 109 AN XY: 727248

Gnomad4 AFR exome AF: 0.00442

Gnomad4 AMR exome AF: 0.000760

Gnomad4 ASJ exome AF: 0.000497

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.00120 AC: 183 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.00105 AC XY: 78 AN XY: 74474

Gnomad4 AFR AF: 0.00402

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000177 Hom.: 0

Bravo AF: 0.00130

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000436 AC: 53

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	13
Dann	Benign	0.67
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.012	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.28	T;T;T
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.74, 0.83	.;P;P
Vest4		0.84
MVP		0.13
MPC		0.35
ClinPred		0.023	T
GERP RS		-0.70
Varity_R		0.31
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs61743401; hg19: chr1-167779982;