9-78325660-G-A

Variant names:

• chr9-78325660-G-A
• rs1411916
• NM_058179.4:c.870-2391G>A

Variant summary

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

The NM_058179.4(PSAT1):​c.870-2391G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 152,176 control chromosomes in the GnomAD database, including 529 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 0.075 (529 hom., cov: 33)
• Consequence: PSAT1 NM_058179.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 6 publications found

Genes affected

PSAT1 (HGNC:19129): (phosphoserine aminotransferase 1) This gene encodes a member of the class-V pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is a phosphoserine aminotransferase and decreased expression may be associated with schizophrenia. Mutations in this gene are also associated with phosphoserine aminotransferase deficiency. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 1, 3, and 8. [provided by RefSeq, Jul 2013]

PSAT1 Gene-Disease associations (from GenCC):

• neurometabolic disorder due to serine deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• PSAT deficiency

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• Neu-Laxova syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058179.4. 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
	PSAT1	NM_058179.4	MANE Select	c.870-2391G>A		intron	N/A	NP_478059.1
	PSAT1	NM_021154.5		c.870-3321G>A		intron	N/A	NP_066977.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSAT1	ENST00000376588.4	TSL:1 MANE Select	c.870-2391G>A		intron	N/A	ENSP00000365773.3
	PSAT1	ENST00000347159.6	TSL:1	c.870-3321G>A		intron	N/A	ENSP00000317606.2

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11422 AN: 152058 Hom.: 529 Cov.: 33

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0448

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0688

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

GnomAD4 genome AF: 0.0751 AC: 11436 AN: 152176 Hom.: 529 Cov.: 33 AF XY: 0.0753 AC XY: 5599 AN XY: 74400

African (AFR) AF: 0.0231 AC: 961 AN: 41536

American (AMR) AF: 0.0624 AC: 954 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3460

East Asian (EAS) AF: 0.0451 AC: 234 AN: 5184

South Asian (SAS) AF: 0.119 AC: 571 AN: 4818

European-Finnish (FIN) AF: 0.102 AC: 1083 AN: 10572

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6993 AN: 68008

Other (OTH) AF: 0.0672 AC: 142 AN: 2114

Alfa AF: 0.0857 Hom.: 988

Bravo AF: 0.0671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.25
DANN	Benign	0.59
PhyloP100		-2.3
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: rs1411916; hg19: chr9-80940576;