1-119711922-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000641597.1(PHGDH):​c.-101G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 1,213,964 control chromosomes in the GnomAD database, including 317,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44369 hom., cov: 32)
Exomes 𝑓: 0.71 ( 272988 hom. )

Consequence

PHGDH
ENST00000641597.1 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.563
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 1-119711922-G-C is Benign according to our data. Variant chr1-119711922-G-C is described in ClinVar as [Benign]. Clinvar id is 292300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-119711922-G-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHGDHNM_006623.4 linkuse as main transcript upstream_gene_variant ENST00000641023.2
PHGDHXM_011541226.3 linkuse as main transcript upstream_gene_variant
PHGDHXR_007058634.1 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHGDHENST00000641023.2 linkuse as main transcript upstream_gene_variant NM_006623.4 P1

Frequencies

GnomAD3 genomes
AF:
0.757
AC:
115181
AN:
152056
Hom.:
44316
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.885
Gnomad AMI
AF:
0.683
Gnomad AMR
AF:
0.742
Gnomad ASJ
AF:
0.662
Gnomad EAS
AF:
0.943
Gnomad SAS
AF:
0.765
Gnomad FIN
AF:
0.673
Gnomad MID
AF:
0.722
Gnomad NFE
AF:
0.688
Gnomad OTH
AF:
0.756
GnomAD4 exome
AF:
0.715
AC:
759073
AN:
1061790
Hom.:
272988
Cov.:
14
AF XY:
0.715
AC XY:
390416
AN XY:
546254
show subpopulations
Gnomad4 AFR exome
AF:
0.897
Gnomad4 AMR exome
AF:
0.707
Gnomad4 ASJ exome
AF:
0.664
Gnomad4 EAS exome
AF:
0.939
Gnomad4 SAS exome
AF:
0.755
Gnomad4 FIN exome
AF:
0.669
Gnomad4 NFE exome
AF:
0.698
Gnomad4 OTH exome
AF:
0.718
GnomAD4 genome
AF:
0.758
AC:
115293
AN:
152174
Hom.:
44369
Cov.:
32
AF XY:
0.759
AC XY:
56431
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.885
Gnomad4 AMR
AF:
0.742
Gnomad4 ASJ
AF:
0.662
Gnomad4 EAS
AF:
0.943
Gnomad4 SAS
AF:
0.766
Gnomad4 FIN
AF:
0.673
Gnomad4 NFE
AF:
0.688
Gnomad4 OTH
AF:
0.760
Alfa
AF:
0.624
Hom.:
1752
Bravo
AF:
0.767
Asia WGS
AF:
0.821
AC:
2856
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

PHGDH deficiency Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 08, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMar 08, 2021- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Neu-Laxova syndrome 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 08, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.96
DANN
Benign
0.47

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.

Other links and lift over

dbSNP: rs562038; hg19: chr1-120254545; COSMIC: COSV65582685; COSMIC: COSV65582685; API