Genetic Variant NM_016556.4:c.383A>C (chr17-42573578-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016556.4(PSMC3IP):c.383A>C(p.Lys128Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K128R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PSMC3IP
NM_016556.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.129

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

ovarian dysgenesis 3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
46 XX gonadal dysgenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PSMC3IP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07013294).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016556.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMC3IP	NM_016556.4	MANE Select	c.383A>C	p.Lys128Thr	missense	Exon 5 of 8	NP_057640.1	Q9P2W1-1
PSMC3IP	NM_013290.7		c.347A>C	p.Lys116Thr	missense	Exon 5 of 8	NP_037422.2
PSMC3IP	NM_001256014.2		c.194A>C	p.Lys65Thr	missense	Exon 4 of 7	NP_001242943.1	K7ERB6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSMC3IP	ENST00000393795.8	TSL:1 MANE Select	c.383A>C	p.Lys128Thr	missense	Exon 5 of 8	ENSP00000377384.2	Q9P2W1-1
PSMC3IP	ENST00000253789.9	TSL:1	c.347A>C	p.Lys116Thr	missense	Exon 5 of 8	ENSP00000253789.4	Q9P2W1-2
PSMC3IP	ENST00000587209.5	TSL:1	c.194A>C	p.Lys65Thr	missense	Exon 4 of 7	ENSP00000468188.1	K7ERB6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111982

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.090

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.77

M_CAP

Benign

0.020

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

0.13

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

REVEL

Benign

0.043

Sift

Benign

0.18

Sift4G

Benign

0.38

Polyphen

0.0020

Vest4

0.32

MutPred

0.50

Loss of ubiquitination at K128 (P = 0.0034)

MVP

0.56

MPC

0.19

ClinPred

0.056

GERP RS

-0.0028

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.28

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over