1-167856368-A-C

Position:

• chr1-167856368-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018417.6(ADCY10):​c.1968T>G​(p.Phe656Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F656F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADCY10 NM_018417.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.1968T>G	p.Phe656Leu	missense_variant	17/33	ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.1968T>G	p.Phe656Leu	missense_variant	17/33	1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.1692T>G	p.Phe564Leu	missense_variant	17/33	1
ADCY10	ENST00000545172.5	c.1509T>G	p.Phe503Leu	missense_variant	14/30	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.12	.;T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	2.0	.;M;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Uncertain	0.38
Sift	Benign	0.057	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.82, 0.88	.;P;P
Vest4		0.64
MutPred		0.49		.;Gain of ubiquitination at K659 (P = 0.143);.;
MVP		0.20
MPC		0.48
ClinPred		0.97	D
GERP RS		-7.4
Varity_R		0.27
gMVP		0.32

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: rs2071922; hg19: chr1-167825606;