rs61744944

Variant names:

• chr9-15468635-T-A
• rs61744944
• NM_033222.5:c.1415A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-15468635-T-A
• chr9-15468635-T-C
• chr9-15468635-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033222.5(PSIP1):​c.1415A>T​(p.Gln472Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00321 in 1,613,878 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (75 hom.)
• Consequence: PSIP1 NM_033222.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.89
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024690926).
• BP6: Variant 9-15468635-T-A is Benign according to our data. Variant chr9-15468635-T-A is described in ClinVar as Benign. ClinVar VariationId is 790063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0548 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSIP1	NM_033222.5	MANE Select	c.1415A>T	p.Gln472Leu	missense	Exon 14 of 16	NP_150091.2
	PSIP1	NM_001128217.3		c.1415A>T	p.Gln472Leu	missense	Exon 14 of 16	NP_001121689.1	O75475-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSIP1	ENST00000380733.9	TSL:1 MANE Select	c.1415A>T	p.Gln472Leu	missense	Exon 14 of 16	ENSP00000370109.4	O75475-1
	PSIP1	ENST00000380738.8	TSL:1	c.1415A>T	p.Gln472Leu	missense	Exon 14 of 16	ENSP00000370114.4	O75475-1
	PSIP1	ENST00000950213.1		c.1451A>T	p.Gln484Leu	missense	Exon 14 of 16	ENSP00000620272.1

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2531 AN: 152204 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00870

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00440 AC: 1106 AN: 251186 AF XY: 0.00325

Gnomad AFR exome AF: 0.0572

Gnomad AMR exome AF: 0.00353

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00181 AC: 2645 AN: 1461556 Hom.: 75 Cov.: 32 AF XY: 0.00155 AC XY: 1130 AN XY: 727092

African (AFR) AF: 0.0580 AC: 1941 AN: 33470

American (AMR) AF: 0.00414 AC: 185 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5766

European-Non Finnish (NFE) AF: 0.000200 AC: 222 AN: 1111748

Other (OTH) AF: 0.00437 AC: 264 AN: 60390

GnomAD4 genome AF: 0.0167 AC: 2541 AN: 152322 Hom.: 60 Cov.: 32 AF XY: 0.0160 AC XY: 1195 AN XY: 74500

African (AFR) AF: 0.0567 AC: 2357 AN: 41566

American (AMR) AF: 0.00869 AC: 133 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68026

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.00116 Hom.: 2

Bravo AF: 0.0195

ESP6500AA AF: 0.0574 AC: 253

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00559 AC: 679

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.046
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.024
Sift	Uncertain	0.012	D
Sift4G	Benign	0.25	T
Polyphen		0.079	B
Vest4		0.44
MVP		0.41
MPC		0.13
ClinPred		0.018	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.17
Mutation Taster		=97/3	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: rs61744944; hg19: chr9-15468633; COSMIC: COSV99062547; COSMIC: COSV99062547;