7-99968341-C-T

Variant names:

• chr7-99968341-C-T
• rs1195895154
• NM_001185.4:c.427G>A

Variant summary

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

The NM_001185.4(AZGP1):​c.427G>A​(p.Asp143Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D143H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AZGP1 NM_001185.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92
• 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.427G>A	p.Asp143Asn	missense	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.427G>A	p.Asp143Asn	missense	Exon 3 of 4	ENSP00000292401.4	P25311
	AZGP1	ENST00000411734.1	TSL:1	c.418G>A	p.Asp140Asn	missense	Exon 3 of 3	ENSP00000396093.1	C9JEV0
	AZGP1	ENST00000868286.1		c.514G>A	p.Asp172Asn	missense	Exon 4 of 5	ENSP00000538345.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 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: 44724

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: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0023	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		2.9
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.15
Sift	Benign	0.060	T
Sift4G	Benign	0.077	T
Polyphen		0.049	B
Vest4		0.28
MutPred		0.82		Gain of methylation at K142 (P = 0.0643)
MVP		0.25
MPC		0.24
ClinPred		0.38	T
GERP RS		1.9
Varity_R		0.20
gMVP		0.36
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs1195895154; hg19: chr7-99565964;