7-99971761-A-G

Position:

• chr7-99971761-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001185.4(AZGP1):​c.322T>C​(p.Tyr108His) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AZGP1 NM_001185.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

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]

AZGP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AZGP1	NM_001185.4	c.322T>C	p.Tyr108His	missense_variant	2/4	ENST00000292401.9	NP_001176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AZGP1	ENST00000292401.9	c.322T>C	p.Tyr108His	missense_variant	2/4	1	NM_001185.4	ENSP00000292401.4
AZGP1	ENST00000411734.1	c.313T>C	p.Tyr105His	missense_variant	2/3	1		ENSP00000396093.1
AZGP1	ENST00000419575.1	c.138+94T>C		intron_variant		3		ENSP00000389942.1
AZGP1	ENST00000495765.1	n.344T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jul 19, 2022

The c.322T>C (p.Y108H) alteration is located in exon 2 (coding exon 2) of the AZGP1 gene. This alteration results from a T to C substitution at nucleotide position 322, causing the tyrosine (Y) at amino acid position 108 to be replaced by a histidine (H). 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	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	0.098
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0015	T
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.083
Sift	Pathogenic	0.0	D;T
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.28
MutPred		0.83		Gain of disorder (P = 0.0226);.;
MVP		0.23
MPC		0.62
ClinPred		0.99	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.62
gMVP		0.64

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: chr7-99569384;