1-119712503-A-G

Variant names:

• chr1-119712503-A-G
• rs478093
• NM_006623.4:c.138+343A>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+343A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 350,550 control chromosomes in the GnomAD database, including 92,835 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 0.73 (41463 hom., cov: 35)
  • Exomes 𝑓: 0.72 (51372 hom.)
• Consequence: PHGDH NM_006623.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHGDH	NM_006623.4	c.138+343A>G		intron_variant	Intron 1 of 11	ENST00000641023.2	NP_006614.2
PHGDH	XM_011541226.3	c.138+343A>G		intron_variant	Intron 1 of 13		XP_011539528.1
PHGDH	XR_007058634.1	n.227+343A>G		intron_variant	Intron 1 of 7
PHGDH	XM_011541227.3	c.-296A>G		upstream_gene_variant			XP_011539529.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHGDH	ENST00000641023.2	c.138+343A>G		intron_variant	Intron 1 of 11		NM_006623.4	ENSP00000493175.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111792 AN: 152122 Hom.: 41423 Cov.: 35

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.742

GnomAD4 exome AF: 0.715 AC: 141856 AN: 198312 Hom.: 51372 Cov.: 0 AF XY: 0.720 AC XY: 77329 AN XY: 107464

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.711

Gnomad4 ASJ exome AF: 0.665

Gnomad4 EAS exome AF: 0.945

Gnomad4 SAS exome AF: 0.752

Gnomad4 FIN exome AF: 0.664

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.692

GnomAD4 genome AF: 0.735 AC: 111888 AN: 152238 Hom.: 41463 Cov.: 35 AF XY: 0.737 AC XY: 54837 AN XY: 74418

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.745

Alfa AF: 0.714 Hom.: 6548

Bravo AF: 0.740

Asia WGS AF: 0.809 AC: 2806 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.42

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: rs478093; hg19: chr1-120255126;