Variant 2-232407381-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_031313.3(ALPG):c.280C>T(p.Pro94Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,613,872 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 9 hom., cov: 31)

Exomes 𝑓: 0.010 ( 117 hom. )

Consequence

ALPG
NM_031313.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.37

Variant links:

Genes affected

ALPG (HGNC:441): (alkaline phosphatase, germ cell) There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The product of this gene is a membrane bound glycosylated enzyme, localized to testis, thymus and certain germ cell tumors, that is closely related to both the placental and intestinal forms of alkaline phosphatase. [provided by RefSeq, Jul 2008]

ALPG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03668204).

BP6

Variant 2-232407381-C-T is Benign according to our data. Variant chr2-232407381-C-T is described in ClinVar as [Benign]. Clinvar id is 771848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPG	NM_031313.3 linkuse as main transcript	c.280C>T	p.Pro94Ser	missense_variant	3/11	ENST00000295453.8	NP_112603.2	P10696

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPG	ENST00000295453.8 linkuse as main transcript	c.280C>T	p.Pro94Ser	missense_variant	3/11	1	NM_031313.3	ENSP00000295453.3		P10696

Frequencies

GnomAD3 genomes

AF:

0.00722

AC:

1097

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.00551

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000628

Gnomad FIN

AF:

0.00612

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00653

AC:

1641

AN:

251162

Hom.:

AF XY:

0.00666

AC XY:

905

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000752

Gnomad FIN exome

AF:

0.00439

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.0104

AC:

15199

AN:

1461720

Hom.:

117

Cov.:

AF XY:

0.0102

AC XY:

7432

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00376

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000592

Gnomad4 FIN exome

AF:

0.00519

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.00858

GnomAD4 genome

AF:

0.00720

AC:

1096

AN:

152152

Hom.:

Cov.:

AF XY:

0.00691

AC XY:

514

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00550

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000629

Gnomad4 FIN

AF:

0.00612

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00992

Hom.:

Bravo

AF:

0.00708

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0120

AC:

103

ExAC

AF:

0.00713

AC:

865

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.0123

EpiControl

AF:

0.0123

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.037

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

3.7

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-7.5

REVEL

Pathogenic

0.70

Sift

Uncertain

0.012

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.86

MVP

0.95

MPC

0.48

ClinPred

0.087

GERP RS

2.0

Varity_R

0.72

gMVP

0.85

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