chr18-907709-A-T

Position:

• chr18-907709-A-T

Variant summary

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

The NM_001099733.2(ADCYAP1):​c.161A>T​(p.Asp54Val) 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. 14/20 in silico tools predict 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. D54G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADCYAP1 NM_001099733.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

Genes affected

ADCYAP1 (HGNC:241): (adenylate cyclase activating polypeptide 1) This gene encodes a secreted proprotein that is further processed into multiple mature peptides. These peptides stimulate adenylate cyclase and increase cyclic adenosine monophosphate (cAMP) levels, resulting in the transcriptional activation of target genes. The products of this gene are key mediators of neuroendocrine stress responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

(HGNC:):

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=0.09868628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCYAP1	NM_001099733.2	c.161A>T	p.Asp54Val	missense_variant	3/5	ENST00000450565.8
ADCYAP1	NM_001117.5	c.161A>T	p.Asp54Val	missense_variant	2/4
ADCYAP1	XM_005258081.5	c.578A>T	p.Asp193Val	missense_variant	4/6
ADCYAP1	XM_047437288.1	c.161A>T	p.Asp54Val	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCYAP1	ENST00000450565.8	c.161A>T	p.Asp54Val	missense_variant	3/5	1	NM_001099733.2	P1
ADCYAP1	ENST00000579794.1	c.161A>T	p.Asp54Val	missense_variant	2/4	1		P1
ADCYAP1	ENST00000269200.5	n.159A>T		non_coding_transcript_exon_variant	1/3	2
	ENST00000582554.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.56
DEOGEN2	Benign	0.29	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	0.73	N;N
PrimateAI	Benign	0.48	T
REVEL	Benign	0.12
Sift4G	Benign	0.088	T;T
Polyphen		0.0	B;B
Vest4		0.22
MutPred		0.12		Gain of glycosylation at P59 (P = 0.0732);Gain of glycosylation at P59 (P = 0.0732);
MVP		0.66
MPC		0.83
ClinPred		0.091	T
GERP RS		4.0
Varity_R		0.12
gMVP		0.27

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: rs2856966; hg19: chr18-907710;