1-119742923-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006623.4(PHGDH):c.1326G>A(p.Thr442Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,613,196 control chromosomes in the GnomAD database, including 376,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T442T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.70 ( 37609 hom., cov: 34)

Exomes 𝑓: 0.68 ( 338873 hom. )

Consequence

PHGDH
NM_006623.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -4.91

Publications

27 publications found

Variant links:

Genes affected

PHGDH (HGNC:8923): (phosphoglycerate dehydrogenase) This gene encodes the enzyme which is involved in the early steps of L-serine synthesis in animal cells. L-serine is required for D-serine and other amino acid synthesis. The enzyme requires NAD/NADH as a cofactor and forms homotetramers for activity. Mutations in this gene have been found in a family with congenital microcephaly, psychomotor retardation and other symptoms. Multiple alternatively spliced transcript variants have been found, however the full-length nature of most are not known. [provided by RefSeq, Aug 2011]

PHGDH Gene-Disease associations (from GenCC):

neurometabolic disorder due to serine deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
PHGDH deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
Neu-Laxova syndrome 1
Inheritance: AR Classification: MODERATE Submitted by: G2P
Neu-Laxova syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PHGDH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.60891E-7).

BP6

Variant 1-119742923-G-A is Benign according to our data. Variant chr1-119742923-G-A is described in ClinVar as Benign. ClinVar VariationId is 292321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006623.4. 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
	PHGDH	NM_006623.4	MANE Select	c.1326G>A	p.Thr442Thr	synonymous	Exon 11 of 12	NP_006614.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHGDH	ENST00000641023.2	MANE Select	c.1326G>A	p.Thr442Thr	synonymous	Exon 11 of 12	ENSP00000493175.1	O43175
PHGDH	ENST00000369409.9	TSL:1	c.1326G>A	p.Thr442Thr	synonymous	Exon 11 of 12	ENSP00000358417.5	A0A2C9F2M7
PHGDH	ENST00000641074.1		c.1195G>A	p.Ala399Thr	missense	Exon 10 of 11	ENSP00000493446.1	A0A286YFL2

Frequencies

GnomAD3 genomes

AF:

0.700

AC:

106465

AN:

152080

Hom.:

37558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.757

Gnomad AMI

AF:

0.601

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.789

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.798

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.727

GnomAD2 exomes

AF:

0.691

AC:

173491

AN:

251152

AF XY:

0.699

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.686

Gnomad ASJ exome

AF:

0.795

Gnomad EAS exome

AF:

0.605

Gnomad FIN exome

AF:

0.573

Gnomad NFE exome

AF:

0.679

Gnomad OTH exome

AF:

0.699

GnomAD4 exome

AF:

0.679

AC:

991360

AN:

1460998

Hom.:

338873

Cov.:

AF XY:

0.684

AC XY:

496867

AN XY:

726846

show subpopulations

African (AFR)

AF:

0.754

AC:

25221

AN:

33466

American (AMR)

AF:

0.691

AC:

30892

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.794

AC:

20742

AN:

26136

East Asian (EAS)

AF:

0.596

AC:

23651

AN:

39690

South Asian (SAS)

AF:

0.804

AC:

69364

AN:

86246

European-Finnish (FIN)

AF:

0.579

AC:

30926

AN:

53414

Middle Eastern (MID)

AF:

0.823

AC:

4743

AN:

5764

European-Non Finnish (NFE)

AF:

0.670

AC:

744552

AN:

1111202

Other (OTH)

AF:

0.684

AC:

41269

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

18027

36054

54081

72108

90135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19264

38528

57792

77056

96320

<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:

0.700

AC:

106559

AN:

152198

Hom.:

37609

Cov.:

AF XY:

0.699

AC XY:

51987

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.758

AC:

31481

AN:

41544

American (AMR)

AF:

0.729

AC:

11161

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.789

AC:

2741

AN:

3472

East Asian (EAS)

AF:

0.603

AC:

3105

AN:

5152

South Asian (SAS)

AF:

0.798

AC:

3857

AN:

4832

European-Finnish (FIN)

AF:

0.573

AC:

6066

AN:

10586

Middle Eastern (MID)

AF:

0.816

AC:

240

AN:

294

European-Non Finnish (NFE)

AF:

0.674

AC:

45836

AN:

67994

Other (OTH)

AF:

0.722

AC:

1524

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1658

3317

4975

6634

8292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<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:

0.688

Hom.:

149901

Bravo

AF:

0.712

TwinsUK

AF:

0.659

AC:

2444

ALSPAC

AF:

0.676

AC:

2607

ESP6500AA

AF:

0.752

AC:

3313

ESP6500EA

AF:

0.683

AC:

5870

ExAC

AF:

0.692

AC:

83997

Asia WGS

AF:

0.678

AC:

2358

AN:

3478

EpiCase

AF:

0.699

EpiControl

AF:

0.710

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

PHGDH deficiency (5)

not provided (4)

Neu-Laxova syndrome 1 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.27

(source)

DANN

Benign

0.37

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.28

MetaRNN

Benign

9.6e-7

PhyloP100

-4.9

GERP RS

-12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over