NM_033222.5:c.1432C>G

Variant names:

• chr9-15466848-G-C
• rs35678110
• NM_033222.5:c.1432C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_033222.5(PSIP1):​c.1432C>G​(p.Leu478Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 1,612,400 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00033 (2 hom.)
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0960
• Publications: 6 publications found

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]

SNAPC3 (HGNC:11136): (small nuclear RNA activating complex polypeptide 3) Predicted to enable RNA polymerase III type 3 promoter sequence-specific DNA binding activity and bent DNA binding activity. Predicted to contribute to RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and core promoter sequence-specific DNA binding activity. Predicted to be involved in snRNA transcription by RNA polymerase II and snRNA transcription by RNA polymerase III. Located in nuclear body and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0057834387).
• BP6: Variant 9-15466848-G-C is Benign according to our data. Variant chr9-15466848-G-C is described in ClinVar as Benign. ClinVar VariationId is 716195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 391 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033222.5. 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
	PSIP1	NM_033222.5	MANE Select	c.1432C>G	p.Leu478Val	missense	Exon 15 of 16	NP_150091.2
	PSIP1	NM_001128217.3		c.1432C>G	p.Leu478Val	missense	Exon 15 of 16	NP_001121689.1
	SNAPC3	NM_001369648.2		c.*5181G>C		downstream_gene	N/A	NP_001356577.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSIP1	ENST00000380733.9	TSL:1 MANE Select	c.1432C>G	p.Leu478Val	missense	Exon 15 of 16	ENSP00000370109.4
	PSIP1	ENST00000380738.8	TSL:1	c.1432C>G	p.Leu478Val	missense	Exon 15 of 16	ENSP00000370114.4

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 390 AN: 152138 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00867

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000843 AC: 210 AN: 249218 AF XY: 0.000623

Gnomad AFR exome AF: 0.00935

Gnomad AMR exome AF: 0.000799

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000328 AC: 479 AN: 1460144 Hom.: 2 Cov.: 30 AF XY: 0.000266 AC XY: 193 AN XY: 726374

African (AFR) AF: 0.00797 AC: 266 AN: 33368

American (AMR) AF: 0.000857 AC: 38 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.000379 AC: 15 AN: 39618

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85850

European-Finnish (FIN) AF: 0.000356 AC: 19 AN: 53396

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000963 AC: 107 AN: 1111360

Other (OTH) AF: 0.000514 AC: 31 AN: 60322

GnomAD4 genome AF: 0.00257 AC: 391 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.00265 AC XY: 197 AN XY: 74450

African (AFR) AF: 0.00867 AC: 360 AN: 41534

American (AMR) AF: 0.000588 AC: 9 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000490 Hom.: 0

Bravo AF: 0.00299

ESP6500AA AF: 0.00976 AC: 43

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000988 AC: 120

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.096
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.047
Sift	Benign	0.84	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.17
MVP		0.24
MPC		0.13
ClinPred		0.0054	T
GERP RS		0.048
Varity_R		0.038
gMVP		0.071
Mutation Taster		=100/0	polymorphism

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: rs35678110; hg19: chr9-15466846;