9-15486060-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_033222.5(PSIP1):c.402T>C(p.Thr134=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,603,266 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (3 hom.)
• Consequence: PSIP1 NM_033222.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.41

Genes affected

PSIP1 (HGNC:9527): (PC4 and SRSF1 interacting protein 1) Enables DNA-binding transcription factor binding activity; chromatin binding activity; and transcription coactivator activity. Involved in mRNA 5'-splice site recognition and positive regulation of transcription by RNA polymerase II. Located in heterochromatin; nuclear periphery; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 9-15486060-A-G is Benign according to our data. Variant chr9-15486060-A-G is described in ClinVar as [Benign]. Clinvar id is 711507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.4 with no splicing effect.
• BS2: High AC in GnomAd at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSIP1	NM_033222.5	c.402T>C	p.Thr134=	synonymous_variant	6/16	ENST00000380733.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSIP1	ENST00000380733.9	c.402T>C	p.Thr134=	synonymous_variant	6/16	1	NM_033222.5	P1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000427 AC: 105 AN: 246094 Hom.: 1 AF XY: 0.000610 AC XY: 81 AN XY: 132816

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000180

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.000166

Gnomad SAS exome AF: 0.00235

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000223

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.000230 AC: 334 AN: 1451008 Hom.: 3 Cov.: 29 AF XY: 0.000291 AC XY: 210 AN XY: 721888

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.000161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000758

Gnomad4 SAS exome AF: 0.00223

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.0000896

Gnomad4 OTH exome AF: 0.000416

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74452

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.000140

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 02, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	11
Dann	Benign	0.88

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: rs139433616; hg19: chr9-15486058;