Genetic Variant ALPI:p.Arg154Gln (chr2-232457059-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001631.5(ALPI):c.461G>A(p.Arg154Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000363 in 1,613,514 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

ALPI
NM_001631.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95

Variant links:

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]

ALPI links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016466975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPI	NM_001631.5 link	c.461G>A	p.Arg154Gln	missense_variant	Exon 4 of 11	ENST00000295463.4	NP_001622.2	P09923A0A024R4A2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ALPI	ENST00000295463.4 link	c.461G>A	p.Arg154Gln	missense_variant	Exon 4 of 11	1	NM_001631.5	ENSP00000295463.3	P09923
ALPI	ENST00000457560.1 link	n.*390G>A		non_coding_transcript_exon_variant	Exon 3 of 10	5		ENSP00000413068.1	F8WEQ0
ALPI	ENST00000457560.1 link	n.*390G>A		3_prime_UTR_variant	Exon 3 of 10	5		ENSP00000413068.1	F8WEQ0

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000556

AC:

139

AN:

250200

Hom.:

AF XY:

0.000583

AC XY:

AN XY:

135478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.000349

AC:

510

AN:

1461180

Hom.:

Cov.:

AF XY:

0.000344

AC XY:

250

AN XY:

726890

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0126

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000845

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000492

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000749

Hom.:

Bravo

AF:

0.000468

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000461

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Mar 04, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Uncertain

0.67

Eigen

Benign

-0.090

Eigen_PC

Benign

-0.065

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.83

M_CAP

Benign

0.046

MetaRNN

Benign

0.016

MetaSVM

Uncertain

0.0097

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.40

Sift

Benign

0.54

Sift4G

Benign

0.31

Polyphen

0.77

Vest4

0.22

MVP

0.93

MPC

0.25

ClinPred

0.051

GERP RS

5.5

Varity_R

0.33

gMVP

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over