7-99967015-C-G

Variant names:

• chr7-99967015-C-G
• rs771426823
• NM_001185.4:c.885G>C

Variant summary

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

The NM_001185.4(AZGP1):​c.885G>C​(p.Trp295Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: AZGP1 NM_001185.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.22

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

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
AZGP1	NM_001185.4	c.885G>C	p.Trp295Cys	missense_variant	Exon 4 of 4	ENST00000292401.9	NP_001176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AZGP1	ENST00000292401.9	c.885G>C	p.Trp295Cys	missense_variant	Exon 4 of 4	1	NM_001185.4	ENSP00000292401.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000161 AC: 4 AN: 248734 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134690

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461278 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726864

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000895

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.885G>C (p.W295C) alteration is located in exon 4 (coding exon 4) of the AZGP1 gene. This alteration results from a G to C substitution at nucleotide position 885, causing the tryptophan (W) at amino acid position 295 to be replaced by a cysteine (C). 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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Benign	0.63
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.069
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0065	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-9.6	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.87	P
Vest4		0.53
MutPred		0.61		Gain of catalytic residue at P294 (P = 0.0086);
MVP		0.055
MPC		0.22
ClinPred		0.90	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.52
gMVP		0.75

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: rs771426823; hg19: chr7-99564638;