9-78304891-G-T

Variant names:

• chr9-78304891-G-T
• rs41277897
• NM_058179.4:c.348G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_058179.4(PSAT1):​c.348G>T​(p.Lys116Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. K116K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PSAT1 NM_058179.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 5.45
• Publications: 3 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
• Neu-Laxova syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
• PSAT deficiency

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSAT1	NM_058179.4	MANE Select	c.348G>T	p.Lys116Asn	missense	Exon 4 of 9	NP_478059.1	Q9Y617-1
	PSAT1	NM_021154.5		c.348G>T	p.Lys116Asn	missense	Exon 4 of 8	NP_066977.1	Q9Y617-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSAT1	ENST00000376588.4	TSL:1 MANE Select	c.348G>T	p.Lys116Asn	missense	Exon 4 of 9	ENSP00000365773.3	Q9Y617-1
	PSAT1	ENST00000347159.6	TSL:1	c.348G>T	p.Lys116Asn	missense	Exon 4 of 8	ENSP00000317606.2	Q9Y617-2
	PSAT1	ENST00000906296.1		c.348G>T	p.Lys116Asn	missense	Exon 4 of 9	ENSP00000576355.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D
Eigen	Benign	0.17
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.25
Sift	Benign	0.040	D
Sift4G	Uncertain	0.056	T
Polyphen		0.32	B
Vest4		0.31
MutPred		0.52		Loss of ubiquitination at K116 (P = 0.0199)
MVP		0.81
MPC		0.33
ClinPred		0.86	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.96
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.39		Position offset: 49

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

Other links and lift over

dbSNP: rs41277897; hg19: chr9-80919807;