Genetic Variant NM_031313.3:c.516T>C (chr2-232407885-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_031313.3(ALPG):c.516T>C(p.His172His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,613,438 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 29 hom. )

Consequence

ALPG
NM_031313.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.83

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 2-232407885-T-C is Benign according to our data. Variant chr2-232407885-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 781828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.83 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPG	NM_031313.3 link	c.516T>C	p.His172His	synonymous_variant	Exon 5 of 11	ENST00000295453.8	NP_112603.2	P10696

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPG	ENST00000295453.8 link	c.516T>C	p.His172His	synonymous_variant	Exon 5 of 11	1	NM_031313.3	ENSP00000295453.3		P10696

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

838

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00886

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00504

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00379

AC:

950

AN:

250964

AF XY:

0.00372

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00427

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00394

AC:

5751

AN:

1461182

Hom.:

Cov.:

AF XY:

0.00394

AC XY:

2862

AN XY:

726900

show subpopulations

African (AFR)

AF:

0.00908

AC:

304

AN:

33478

American (AMR)

AF:

0.00132

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

353

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00265

AC:

228

AN:

86186

European-Finnish (FIN)

AF:

0.00125

AC:

AN:

52814

Middle Eastern (MID)

AF:

0.00625

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00398

AC:

4421

AN:

1111996

Other (OTH)

AF:

0.00465

AC:

281

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

504

1009

1513

2018

2522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00554

AC:

844

AN:

152256

Hom.:

Cov.:

AF XY:

0.00523

AC XY:

389

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00900

AC:

374

AN:

41564

American (AMR)

AF:

0.00222

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00271

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00504

AC:

343

AN:

68008

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00475

Hom.:

Bravo

AF:

0.00569

EpiCase

AF:

0.00567

EpiControl

AF:

0.00462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 08, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ALPG: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.23

(source)

DANN

Benign

0.36

PhyloP100

-3.8

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over