chr1-119712042-G-A

Variant names:

• chr1-119712042-G-A
• rs1650717022
• NM_006623.4:c.20G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006623.4(PHGDH):​c.20G>A​(p.Arg7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHGDH NM_006623.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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]

LOC105378937 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16085193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHGDH	NM_006623.4	c.20G>A	p.Arg7Gln	missense_variant	Exon 1 of 12	ENST00000641023.2	NP_006614.2
PHGDH	XM_011541226.3	c.20G>A	p.Arg7Gln	missense_variant	Exon 1 of 14		XP_011539528.1
PHGDH	XR_007058634.1	n.109G>A		non_coding_transcript_exon_variant	Exon 1 of 8
LOC105378937	XR_947757.4	n.-196C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHGDH	ENST00000641023.2	c.20G>A	p.Arg7Gln	missense_variant	Exon 1 of 12		NM_006623.4	ENSP00000493175.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.;T;.;.;.;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.76	.;T;T;T;T;T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.16	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.41	N;.;N;.;.;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.92	.;.;.;.;.;.;N;.
REVEL	Benign	0.20
Sift	Benign	0.21	.;.;.;.;.;.;T;.
Sift4G	Benign	0.24	.;.;.;.;.;.;T;.
Polyphen		0.0	B;.;B;.;.;.;.;.
Vest4		0.093
MutPred		0.62		Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);Loss of MoRF binding (P = 0.0606);
MVP		0.82
MPC		0.28
ClinPred		0.28	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.27

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: rs1650717022; hg19: chr1-120254665;