2-232456685-C-G

Variant names:

• chr2-232456685-C-G
• NM_001631.5:c.290C>G

Variant summary

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

The NM_001631.5(ALPI):​c.290C>G​(p.Ala97Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALPI NM_001631.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60

Genes affected

ALPI (HGNC:437): (alkaline phosphatase, intestinal) There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The intestinal alkaline phosphatase gene encodes a digestive brush-border enzyme. This enzyme is a component of the gut mucosal defense system and is thought to function in the detoxification of lipopolysaccharide, and in the prevention of bacterial translocation in the gut. [provided by RefSeq, Dec 2014]

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
ALPI	NM_001631.5	c.290C>G	p.Ala97Gly	missense_variant	Exon 3 of 11	ENST00000295463.4	NP_001622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPI	ENST00000295463.4	c.290C>G	p.Ala97Gly	missense_variant	Exon 3 of 11	1	NM_001631.5	ENSP00000295463.3
ALPI	ENST00000457560.1	n.*219C>G		non_coding_transcript_exon_variant	Exon 2 of 10	5		ENSP00000413068.1
ALPI	ENST00000457560.1	n.*219C>G		3_prime_UTR_variant	Exon 2 of 10	5		ENSP00000413068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290C>G (p.A97G) alteration is located in exon 3 (coding exon 3) of the ALPI gene. This alteration results from a C to G substitution at nucleotide position 290, causing the alanine (A) at amino acid position 97 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Benign	0.93
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	0.16
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	0.52	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.64
Sift	Benign	0.30	T
Sift4G	Benign	0.61	T
Polyphen		0.80	P
Vest4		0.53
MutPred		0.75		Gain of sheet (P = 0.0073);
MVP		0.84
MPC		0.22
ClinPred		0.84	D
GERP RS		4.7
Varity_R		0.29
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-233321395;