rs16859886

Variant names:

• chr1-167896633-G-A
• rs16859886
• NM_018417.6:c.701C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-167896633-G-A
• chr1-167896633-G-C
• chr1-167896633-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_018417.6(ADCY10):​c.701C>T​(p.Thr234Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 1,611,658 control chromosomes in the GnomAD database, including 5,435 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T234T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.095 (824 hom., cov: 31)
  • Exomes 𝑓: 0.075 (4611 hom.)
• Consequence: ADCY10 NM_018417.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: 1.51
• Publications: 24 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]

DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-167896633-G-A is Benign according to our data. Variant chr1-167896633-G-A is described in ClinVar as Benign. ClinVar VariationId is 1167838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	NM_018417.6	MANE Select	c.701C>T	p.Thr234Met	missense	Exon 7 of 33	NP_060887.2
	ADCY10	NM_001297772.2		c.425C>T	p.Thr142Met	missense	Exon 7 of 33	NP_001284701.1
	ADCY10	NM_001167749.3		c.242C>T	p.Thr81Met	missense	Exon 4 of 30	NP_001161221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	ENST00000367851.9	TSL:1 MANE Select	c.701C>T	p.Thr234Met	missense	Exon 7 of 33	ENSP00000356825.4
	ADCY10	ENST00000367848.1	TSL:1	c.425C>T	p.Thr142Met	missense	Exon 7 of 33	ENSP00000356822.1
	ADCY10	ENST00000545172.5	TSL:2	c.242C>T	p.Thr81Met	missense	Exon 4 of 30	ENSP00000441992.1

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14465 AN: 152054 Hom.: 822 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0825

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.0850

GnomAD2 exomes AF: 0.0701 AC: 17620 AN: 251454 AF XY: 0.0679

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0566

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0783

Gnomad NFE exome AF: 0.0797

Gnomad OTH exome AF: 0.0826

GnomAD4 exome AF: 0.0746 AC: 108871 AN: 1459486 Hom.: 4611 Cov.: 31 AF XY: 0.0729 AC XY: 52962 AN XY: 726160

African (AFR) AF: 0.156 AC: 5195 AN: 33386

American (AMR) AF: 0.0590 AC: 2636 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2657 AN: 26116

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.0254 AC: 2192 AN: 86228

European-Finnish (FIN) AF: 0.0826 AC: 4409 AN: 53400

Middle Eastern (MID) AF: 0.0872 AC: 502 AN: 5760

European-Non Finnish (NFE) AF: 0.0780 AC: 86590 AN: 1109884

Other (OTH) AF: 0.0777 AC: 4688 AN: 60314

GnomAD4 genome AF: 0.0952 AC: 14483 AN: 152172 Hom.: 824 Cov.: 31 AF XY: 0.0934 AC XY: 6946 AN XY: 74390

African (AFR) AF: 0.154 AC: 6394 AN: 41494

American (AMR) AF: 0.0824 AC: 1260 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0237 AC: 114 AN: 4816

European-Finnish (FIN) AF: 0.0728 AC: 771 AN: 10592

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0780 AC: 5307 AN: 68006

Other (OTH) AF: 0.0836 AC: 177 AN: 2116

Alfa AF: 0.0831 Hom.: 1891

Bravo AF: 0.0987

TwinsUK AF: 0.0828 AC: 307

ALSPAC AF: 0.0755 AC: 291

ESP6500AA AF: 0.153 AC: 676

ESP6500EA AF: 0.0801 AC: 689

ExAC AF: 0.0719 AC: 8725

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.0859

EpiControl AF: 0.0869

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	-	Familial idiopathic hypercalciuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.053
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.9	N
PhyloP100		1.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.16
MPC		0.12
ClinPred		0.0048	T
GERP RS		5.3
Varity_R		0.059
gMVP		0.44
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.33		Position offset: -38

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16859886; hg19: chr1-167865871; COSMIC: COSV63241833;