chr1-119714953-A-G

Position:

• chr1-119714953-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHGDH	NM_006623.4	c.138+2793A>G		intron_variant		ENST00000641023.2	NP_006614.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHGDH	ENST00000641023.2	c.138+2793A>G		intron_variant			NM_006623.4	ENSP00000493175	P1

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

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.718

Alfa AF: 0.689 Hom.: 56631

Bravo AF: 0.691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs477992; hg19: chr1-120257576;