7-45574716-A-T

Variant names:

• chr7-45574716-A-T
• NM_021116.4:c.173A>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021116.4(ADCY1):​c.173A>T​(p.Gln58Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000159 in 1,258,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000016 (0 hom.)
• Consequence: ADCY1 NM_021116.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.38

Genes affected

ADCY1 (HGNC:232): (adenylate cyclase 1) This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY1	NM_021116.4	c.173A>T	p.Gln58Leu	missense_variant	Exon 1 of 20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4	c.173A>T	p.Gln58Leu	missense_variant	Exon 1 of 19		XP_005249641.1
ADCY1	XM_005249585.3	c.173A>T	p.Gln58Leu	missense_variant	Exon 1 of 9		XP_005249642.1
ADCY1	NM_001281768.2	c.-330-173A>T		intron_variant	Intron 1 of 9		NP_001268697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12	c.173A>T	p.Gln58Leu	missense_variant	Exon 1 of 20	1	NM_021116.4	ENSP00000297323.7
ADCY1	ENST00000432715.5	c.-330-173A>T		intron_variant	Intron 1 of 9	2		ENSP00000392721.1
ADCY1	ENST00000621543.1	c.-503A>T		upstream_gene_variant		5		ENSP00000479770.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1258616 Hom.: 0 Cov.: 30 AF XY: 0.00000162 AC XY: 1 AN XY: 618170

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: 0.00000196

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	0.34
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.76	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.99	D
Vest4		0.66
MutPred		0.57		Gain of helix (P = 0.0425);
MVP		0.89
MPC		2.1
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.61
gMVP		0.55

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: chr7-45614315;