NM_016556.4:c.338-158G>A

Variant names:

• chr17-42573781-C-T
• rs2292751
• NM_016556.4:c.338-158G>A

Variant summary

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

The NM_016556.4(PSMC3IP):​c.338-158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,499,422 control chromosomes in the GnomAD database, including 228,362 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20671 hom., cov: 33)
  • Exomes 𝑓: 0.55 (207691 hom.)
• Consequence: PSMC3IP NM_016556.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0110
• Publications: 13 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-42573781-C-T is Benign according to our data. Variant chr17-42573781-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMC3IP	NM_016556.4	MANE Select	c.338-158G>A		intron	N/A	NP_057640.1	Q9P2W1-1
	PSMC3IP	NM_013290.7		c.338-194G>A		intron	N/A	NP_037422.2
	PSMC3IP	NM_001256014.2		c.149-158G>A		intron	N/A	NP_001242943.1	K7ERB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMC3IP	ENST00000393795.8	TSL:1 MANE Select	c.338-158G>A		intron	N/A	ENSP00000377384.2	Q9P2W1-1
	PSMC3IP	ENST00000253789.9	TSL:1	c.338-194G>A		intron	N/A	ENSP00000253789.4	Q9P2W1-2
	PSMC3IP	ENST00000587209.5	TSL:1	c.149-158G>A		intron	N/A	ENSP00000468188.1	K7ERB6

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79007 AN: 151976 Hom.: 20644 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.490

GnomAD2 exomes AF: 0.535 AC: 68788 AN: 128650 AF XY: 0.544

Gnomad AFR exome AF: 0.492

Gnomad AMR exome AF: 0.519

Gnomad ASJ exome AF: 0.395

Gnomad EAS exome AF: 0.439

Gnomad FIN exome AF: 0.525

Gnomad NFE exome AF: 0.550

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.553 AC: 745309 AN: 1347328 Hom.: 207691 Cov.: 35 AF XY: 0.555 AC XY: 368930 AN XY: 664802

African (AFR) AF: 0.484 AC: 14512 AN: 30008

American (AMR) AF: 0.518 AC: 16786 AN: 32410

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 9306 AN: 23866

East Asian (EAS) AF: 0.454 AC: 16138 AN: 35580

South Asian (SAS) AF: 0.635 AC: 48405 AN: 76204

European-Finnish (FIN) AF: 0.539 AC: 19269 AN: 35774

Middle Eastern (MID) AF: 0.406 AC: 1587 AN: 3906

European-Non Finnish (NFE) AF: 0.560 AC: 589543 AN: 1053436

Other (OTH) AF: 0.530 AC: 29763 AN: 56144

GnomAD4 genome AF: 0.520 AC: 79077 AN: 152094 Hom.: 20671 Cov.: 33 AF XY: 0.517 AC XY: 38461 AN XY: 74356

African (AFR) AF: 0.494 AC: 20501 AN: 41470

American (AMR) AF: 0.481 AC: 7361 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1354 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2265 AN: 5172

South Asian (SAS) AF: 0.642 AC: 3103 AN: 4832

European-Finnish (FIN) AF: 0.531 AC: 5608 AN: 10564

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37298 AN: 67976

Other (OTH) AF: 0.495 AC: 1046 AN: 2114

Alfa AF: 0.528 Hom.: 36283

Bravo AF: 0.510

Asia WGS AF: 0.589 AC: 2048 AN: 3478

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.4
DANN	Benign	0.77
PhyloP100		-0.011
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2292751; hg19: chr17-40725799; COSMIC: COSV53816639; COSMIC: COSV53816639;