Variant 17-42573638-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016556.4(PSMC3IP):c.338-15C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,612,718 control chromosomes in the GnomAD database, including 255,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25516 hom., cov: 33)

Exomes 𝑓: 0.56 ( 230388 hom. )

Consequence

PSMC3IP
NM_016556.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.556

Variant links:

Genes affected

PSMC3IP (HGNC:17928): (PSMC3 interacting protein) This gene encodes a protein that functions in meiotic recombination. It is a subunit of the PSMC3IP/MND1 complex, which interacts with PSMC3/TBP1 to stimulate DMC1- and RAD51-mediated strand exchange during meiosis. The protein encoded by this gene can also co-activate ligand-driven transcription mediated by estrogen, androgen, glucocorticoid, progesterone, and thyroid nuclear receptors. Mutations in this gene cause XX female gonadal dysgenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2011]

PSMC3IP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-42573638-G-C is Benign according to our data. Variant chr17-42573638-G-C is described in ClinVar as [Benign]. Clinvar id is 1285798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-42573638-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMC3IP	NM_016556.4 linkuse as main transcript	c.338-15C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000393795.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMC3IP	ENST00000393795.8 linkuse as main transcript	c.338-15C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_016556.4	P1	Q9P2W1-1

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

87279

AN:

151964

Hom.:

25488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.685

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.521

GnomAD3 exomes

AF:

0.551

AC:

138494

AN:

251198

Hom.:

38908

AF XY:

0.552

AC XY:

74992

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.535

Gnomad ASJ exome

AF:

0.394

Gnomad EAS exome

AF:

0.441

Gnomad SAS exome

AF:

0.641

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.551

Gnomad OTH exome

AF:

0.506

GnomAD4 exome

AF:

0.559

AC:

816839

AN:

1460636

Hom.:

230388

Cov.:

AF XY:

0.560

AC XY:

406982

AN XY:

726704

show subpopulations

Gnomad4 AFR exome

AF:

0.681

Gnomad4 AMR exome

AF:

0.535

Gnomad4 ASJ exome

AF:

0.392

Gnomad4 EAS exome

AF:

0.453

Gnomad4 SAS exome

AF:

0.637

Gnomad4 FIN exome

AF:

0.540

Gnomad4 NFE exome

AF:

0.561

Gnomad4 OTH exome

AF:

0.544

GnomAD4 genome

AF:

0.574

AC:

87361

AN:

152082

Hom.:

25516

Cov.:

AF XY:

0.570

AC XY:

42405

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.685

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.438

Gnomad4 SAS

AF:

0.643

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.549

Gnomad4 OTH

AF:

0.525

Alfa

AF:

0.440

Hom.:

2097

Bravo

AF:

0.573

Asia WGS

AF:

0.601

AC:

2092

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Ovarian dysgenesis 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Oct 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over