rs982000290

Variant names:

• chr14-24319345-C-G
• rs982000290
• NM_001198568.2:c.2825G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-24319345-C-G
• chr14-24319345-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001198568.2(ADCY4):​c.2825G>C​(p.Gly942Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G942E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADCY4 NM_001198568.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.00
• Publications: 0 publications found

Genes affected

ADCY4 (HGNC:235): (adenylate cyclase 4) This gene encodes a member of the family of adenylate cyclases, which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). Mouse studies show that adenylate cyclase 4, along with adenylate cyclases 2 and 3, is expressed in olfactory cilia, suggesting that several different adenylate cyclases may couple to olfactory receptors and that there may be multiple receptor-mediated mechanisms for the generation of cAMP signals. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29286045).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198568.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY4	NM_001198568.2	MANE Select	c.2825G>C	p.Gly942Ala	missense	Exon 22 of 25	NP_001185497.1	Q8NFM4-1
	ADCY4	NM_001198592.2		c.2825G>C	p.Gly942Ala	missense	Exon 23 of 26	NP_001185521.1	Q8NFM4-1
	ADCY4	NM_139247.4		c.2825G>C	p.Gly942Ala	missense	Exon 23 of 26	NP_640340.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY4	ENST00000418030.7	TSL:1 MANE Select	c.2825G>C	p.Gly942Ala	missense	Exon 22 of 25	ENSP00000393177.2	Q8NFM4-1
	ADCY4	ENST00000554068.6	TSL:1	c.2825G>C	p.Gly942Ala	missense	Exon 23 of 26	ENSP00000452250.2	Q8NFM4-1
	ADCY4	ENST00000554781.5	TSL:1	n.*1507G>C		non_coding_transcript_exon	Exon 22 of 25	ENSP00000450477.1	G3V258

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	0.055
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.0
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.16
Sift	Benign	0.077	T
Sift4G	Benign	0.076	T
Polyphen		0.060	B
Vest4		0.36
MutPred		0.54		Gain of catalytic residue at N938 (P = 0.0241)
MVP		0.75
MPC		1.1
ClinPred		0.86	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.56
Mutation Taster		=62/38	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs982000290; hg19: chr14-24788551;