rs41277897

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-78304891-G-A
• chr9-78304891-G-C
• chr9-78304891-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_058179.4(PSAT1):​c.348G>A​(p.Lys116Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.00996 in 1,613,654 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0092 (20 hom., cov: 33)
  • Exomes 𝑓: 0.010 (163 hom.)
• Consequence: PSAT1 NM_058179.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 9-78304891-G-A is Benign according to our data. Variant chr9-78304891-G-A is described in ClinVar as Benign. ClinVar VariationId is 542040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00922 (1404/152324) while in subpopulation NFE AF = 0.0146 (994/68030). AF 95% confidence interval is 0.0139. There are 20 homozygotes in GnomAd4. There are 692 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR,AD gene

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>A	p.Lys116Lys	synonymous	Exon 4 of 9	NP_478059.1	Q9Y617-1
	PSAT1	NM_021154.5		c.348G>A	p.Lys116Lys	synonymous	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>A	p.Lys116Lys	synonymous	Exon 4 of 9	ENSP00000365773.3	Q9Y617-1
	PSAT1	ENST00000347159.6	TSL:1	c.348G>A	p.Lys116Lys	synonymous	Exon 4 of 8	ENSP00000317606.2	Q9Y617-2
	PSAT1	ENST00000906296.1		c.348G>A	p.Lys116Lys	synonymous	Exon 4 of 9	ENSP00000576355.1

Frequencies

GnomAD3 genomes AF: 0.00921 AC: 1402 AN: 152206 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00911 AC: 2292 AN: 251476 AF XY: 0.00900

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00764

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0183

Gnomad NFE exome AF: 0.0141

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.0100 AC: 14667 AN: 1461330 Hom.: 163 Cov.: 36 AF XY: 0.0101 AC XY: 7346 AN XY: 726986

African (AFR) AF: 0.00123 AC: 41 AN: 33468

American (AMR) AF: 0.00197 AC: 88 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00627 AC: 164 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00255 AC: 220 AN: 86228

European-Finnish (FIN) AF: 0.0201 AC: 1074 AN: 53420

Middle Eastern (MID) AF: 0.000562 AC: 3 AN: 5336

European-Non Finnish (NFE) AF: 0.0113 AC: 12594 AN: 1111980

Other (OTH) AF: 0.00799 AC: 482 AN: 60338

GnomAD4 genome AF: 0.00922 AC: 1404 AN: 152324 Hom.: 20 Cov.: 33 AF XY: 0.00929 AC XY: 692 AN XY: 74476

African (AFR) AF: 0.00132 AC: 55 AN: 41576

American (AMR) AF: 0.00346 AC: 53 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00331 AC: 16 AN: 4832

European-Finnish (FIN) AF: 0.0210 AC: 223 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0146 AC: 994 AN: 68030

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.0131 Hom.: 16

Bravo AF: 0.00706

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0133

EpiControl AF: 0.00806

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Neu-Laxova syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	9.1
DANN	Benign	0.69
PhyloP100		5.5
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.32		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; COSMIC: COSV100716534;