chr1-119714953-A-G

Variant names:

• chr1-119714953-A-G
• rs477992
• NM_006623.4:c.138+2793A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006623.4(PHGDH):​c.138+2793A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,092 control chromosomes in the GnomAD database, including 36,590 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36590 hom., cov: 32)
• Consequence: PHGDH NM_006623.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 37 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.921 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHGDH	NM_006623.4	MANE Select	c.138+2793A>G		intron	N/A	NP_006614.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHGDH	ENST00000641023.2	MANE Select	c.138+2793A>G		intron	N/A	ENSP00000493175.1
	PHGDH	ENST00000369409.9	TSL:1	c.138+2793A>G		intron	N/A	ENSP00000358417.5
	PHGDH	ENST00000641597.1		c.138+2793A>G		intron	N/A	ENSP00000493382.1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105012 AN: 151974 Hom.: 36556 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.714

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.691 AC: 105099 AN: 152092 Hom.: 36590 Cov.: 32 AF XY: 0.695 AC XY: 51642 AN XY: 74342

African (AFR) AF: 0.656 AC: 27189 AN: 41466

American (AMR) AF: 0.715 AC: 10934 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2296 AN: 3472

East Asian (EAS) AF: 0.943 AC: 4883 AN: 5176

South Asian (SAS) AF: 0.764 AC: 3684 AN: 4820

European-Finnish (FIN) AF: 0.673 AC: 7110 AN: 10564

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46658 AN: 67980

Other (OTH) AF: 0.718 AC: 1517 AN: 2114

Alfa AF: 0.689 Hom.: 88084

Bravo AF: 0.691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.38
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs477992; hg19: chr1-120257576;