rs541503

Positions:

• chr1-119665674-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007066508.1(LOC124904390):​n.217-3517T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 151,884 control chromosomes in the GnomAD database, including 8,218 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 0.31 (8218 hom., cov: 30)
• Consequence: LOC124904390 XR_007066508.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

Genes affected

LOC124904390 (HGNC:):

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904390	XR_007066508.1	n.217-3517T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHGDH	ENST00000493622.5	c.-358-3517T>C		intron_variant		5		ENSP00000493433
PHGDH	ENST00000641597.1	c.-615-3520T>C		intron_variant				ENSP00000493382	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46859 AN: 151766 Hom.: 8221 Cov.: 30

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.0557

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.308 AC: 46852 AN: 151884 Hom.: 8218 Cov.: 30 AF XY: 0.305 AC XY: 22635 AN XY: 74210

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.0559

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.300

Alfa AF: 0.340 Hom.: 1599

Bravo AF: 0.297

Asia WGS AF: 0.210 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.84
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs541503; hg19: chr1-120208297; COSMIC: COSV72459174;