rs982000290

Variant names:

• chr14-24319345-C-G
• 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. Variant got 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY4	NM_001198568.2	c.2825G>C	p.Gly942Ala	missense_variant	Exon 22 of 25	ENST00000418030.7	NP_001185497.1
ADCY4	NM_001198592.2	c.2825G>C	p.Gly942Ala	missense_variant	Exon 23 of 26		NP_001185521.1
ADCY4	NM_139247.4	c.2825G>C	p.Gly942Ala	missense_variant	Exon 23 of 26		NP_640340.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY4	ENST00000418030.7	c.2825G>C	p.Gly942Ala	missense_variant	Exon 22 of 25	1	NM_001198568.2	ENSP00000393177.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;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;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.16
Sift	Benign	0.077	T;T;T
Sift4G	Benign	0.076	T;T;T
Polyphen		0.060	B;B;B
Vest4		0.36
MutPred		0.54		Gain of catalytic residue at N938 (P = 0.0241);Gain of catalytic residue at N938 (P = 0.0241);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24788551;