Variant chr17-42574113-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016556.4(PSMC3IP):c.323G>A(p.Arg108His) variant causes a missense change. The variant allele was found at a frequency of 0.000256 in 1,614,152 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 7 hom. )

Consequence

PSMC3IP
NM_016556.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.60

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014217317).

BP6

Variant 17-42574113-C-T is Benign according to our data. Variant chr17-42574113-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMC3IP	NM_016556.4 link	c.323G>A	p.Arg108His	missense_variant	4/8	ENST00000393795.8	NP_057640.1	Q9P2W1-1A0A158RUX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSMC3IP	ENST00000393795.8 link	c.323G>A	p.Arg108His	missense_variant	4/8	1	NM_016556.4	ENSP00000377384.2		Q9P2W1-1

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00288

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000602

AC:

151

AN:

251034

Hom.:

AF XY:

0.000471

AC XY:

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00283

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000233

AC:

341

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

139

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00154

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.000473

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000283

Hom.:

Bravo

AF:

0.000680

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000519

AC:

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 11, 2023	- -

PSMC3IP-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 07, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

T;.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.6

M;M;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

N;N;.

REVEL

Benign

0.21

Sift

Uncertain

0.017

D;D;.

Sift4G

Uncertain

0.050

T;D;T

Polyphen

1.0

D;D;.

Vest4

0.35

MVP

0.47

MPC

0.68

ClinPred

0.055

GERP RS

4.8

Varity_R

0.55

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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