16-50301148-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114.5(ADCY7):c.1302C>G(p.His434Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADCY7 NM_001114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0160

Genes affected

ADCY7 (HGNC:238): (adenylate cyclase 7) This gene encodes a membrane-bound adenylate cyclase that catalyses the formation of cyclic AMP from ATP and is inhibitable by calcium. The product of this gene is a member of the adenylyl cyclase class-4/guanylyl cyclase enzyme family that is characterized by the presence of twelve membrane-spanning domains in its sequences. Several transcript variants have been observed for this gene, but the full-length natures of only two have been determined so far. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18307889).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY7	NM_001114.5	c.1302C>G	p.His434Gln	missense_variant	10/26	ENST00000673801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY7	ENST00000673801.1	c.1302C>G	p.His434Gln	missense_variant	10/26		NM_001114.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

The c.1302C>G (p.H434Q) alteration is located in exon 9 (coding exon 9) of the ADCY7 gene. This alteration results from a C to G substitution at nucleotide position 1302, causing the histidine (H) at amino acid position 434 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	16
Dann	Benign	0.93
DEOGEN2	Uncertain	0.44	T;.;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.66	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.2	L;.;L
MutationTaster	Benign	0.74	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N;.;N
REVEL	Benign	0.15
Sift	Benign	0.19	T;.;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.24
MutPred		0.40		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.76
MPC		0.48
ClinPred		0.22	T
GERP RS		-1.7
Varity_R		0.070
gMVP		0.33

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: chr16-50335059;