Variant 17-42574107-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016556.4(PSMC3IP):c.329T>C(p.Met110Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PSMC3IP
NM_016556.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.51

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37018877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSMC3IP	NM_016556.4 link	c.329T>C	p.Met110Thr	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.329T>C	p.Met110Thr	missense_variant	4/8	1	NM_016556.4	ENSP00000377384.2		Q9P2W1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.329T>C (p.M110T) alteration is located in exon 4 (coding exon 4) of the PSMC3IP gene. This alteration results from a T to C substitution at nucleotide position 329, causing the methionine (M) at amino acid position 110 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.15

T;.;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

N;N;.

REVEL

Benign

0.13

Sift

Uncertain

0.020

D;T;.

Sift4G

Benign

0.61

T;T;T

Polyphen

0.27

B;B;.

Vest4

0.47

MutPred

0.69

Gain of phosphorylation at M110 (P = 0.0396);Gain of phosphorylation at M110 (P = 0.0396);.;

MVP

0.42

MPC

0.28

ClinPred

0.72

GERP RS

5.7

Varity_R

0.50

gMVP

0.46

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over