rs375706788

Variant names:

• chr7-99968332-C-A
• rs375706788
• NM_001185.4:c.436G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-99968332-C-A
• chr7-99968332-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001185.4(AZGP1):​c.436G>T​(p.Glu146*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AZGP1 NM_001185.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 0 publications found

Genes affected

AZGP1 (HGNC:910): (alpha-2-glycoprotein 1, zinc-binding) Involved in cell adhesion and detection of chemical stimulus involved in sensory perception of bitter taste. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001185.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AZGP1	NM_001185.4	MANE Select	c.436G>T	p.Glu146*	stop_gained	Exon 3 of 4	NP_001176.1	P25311

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AZGP1	ENST00000292401.9	TSL:1 MANE Select	c.436G>T	p.Glu146*	stop_gained	Exon 3 of 4	ENSP00000292401.4	P25311
	AZGP1	ENST00000411734.1	TSL:1	c.427G>T	p.Glu143*	stop_gained	Exon 3 of 3	ENSP00000396093.1	C9JEV0
	AZGP1	ENST00000868286.1		c.523G>T	p.Glu175*	stop_gained	Exon 4 of 5	ENSP00000538345.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Benign	0.93
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.017	N
PhyloP100		-0.85
Vest4		0.74
GERP RS		-0.25
Mutation Taster		=69/131	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs375706788; hg19: chr7-99565955;