chr8-130780534-A-T

Variant names:

• chr8-130780534-A-T
• NM_001115.3:c.3612T>A

Variant summary

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

The NM_001115.3(ADCY8):​c.3612T>A​(p.Asn1204Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADCY8 NM_001115.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82

Genes affected

ADCY8 (HGNC:239): (adenylate cyclase 8) Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. The enzymatic activity is under the control of several hormones, and different polypeptides participate in the transduction of the signal from the receptor to the catalytic moiety. Stimulatory or inhibitory receptors (Rs and Ri) interact with G proteins (Gs and Gi) that exhibit GTPase activity and they modulate the activity of the catalytic subunit of the adenylyl cyclase [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.3612T>A	p.Asn1204Lys	missense_variant	Exon 18 of 18	ENST00000286355.10	NP_001106.1
ADCY8	XM_005250769.4	c.3522T>A	p.Asn1174Lys	missense_variant	Exon 17 of 17		XP_005250826.1
ADCY8	XM_006716501.4	c.3414T>A	p.Asn1138Lys	missense_variant	Exon 17 of 17		XP_006716564.1
ADCY8	XM_017013006.2	c.3324T>A	p.Asn1108Lys	missense_variant	Exon 16 of 16		XP_016868495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.3612T>A	p.Asn1204Lys	missense_variant	Exon 18 of 18	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.3219T>A	p.Asn1073Lys	missense_variant	Exon 15 of 15	1		ENSP00000367161.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727236

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.0023	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.23
Sift	Benign	0.79	T;T
Sift4G	Benign	0.88	T;T
Polyphen		0.025	B;B
Vest4		0.72
MutPred		0.34		Loss of loop (P = 0.0203);.;
MVP		0.74
MPC		0.48
ClinPred		0.36	T
GERP RS		2.9
Varity_R		0.11
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-131792780;