17-42573638-G-C

Variant names:

• chr17-42573638-G-C
• rs2292752
• NM_016556.4:c.338-15C>G

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.338-15C>G variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.556
• Publications: 25 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=-0.83).
• BP6: Variant 17-42573638-G-C is Benign according to our data. Variant chr17-42573638-G-C is described in ClinVar as Benign. ClinVar VariationId is 1285798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 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.338-15C>G		intron	N/A	NP_057640.1	Q9P2W1-1
	PSMC3IP	NM_013290.7		c.338-51C>G		intron	N/A	NP_037422.2
	PSMC3IP	NM_001256014.2		c.149-15C>G		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.338-15C>G		intron	N/A	ENSP00000377384.2	Q9P2W1-1
	PSMC3IP	ENST00000253789.9	TSL:1	c.338-51C>G		intron	N/A	ENSP00000253789.4	Q9P2W1-2
	PSMC3IP	ENST00000587209.5	TSL:1	c.149-15C>G		intron	N/A	ENSP00000468188.1	K7ERB6

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87279 AN: 151964 Hom.: 25488 Cov.: 33

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

GnomAD2 exomes AF: 0.551 AC: 138494 AN: 251198 AF XY: 0.552

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 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.: 55 AF XY: 0.560 AC XY: 406982 AN XY: 726704

African (AFR) AF: 0.681 AC: 22757 AN: 33428

American (AMR) AF: 0.535 AC: 23923 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 10230 AN: 26128

East Asian (EAS) AF: 0.453 AC: 17978 AN: 39692

South Asian (SAS) AF: 0.637 AC: 54968 AN: 86228

European-Finnish (FIN) AF: 0.540 AC: 28852 AN: 53390

Middle Eastern (MID) AF: 0.417 AC: 2401 AN: 5756

European-Non Finnish (NFE) AF: 0.561 AC: 622891 AN: 1110942

Other (OTH) AF: 0.544 AC: 32839 AN: 60360

GnomAD4 genome AF: 0.574 AC: 87361 AN: 152082 Hom.: 25516 Cov.: 33 AF XY: 0.570 AC XY: 42405 AN XY: 74358

African (AFR) AF: 0.685 AC: 28384 AN: 41452

American (AMR) AF: 0.500 AC: 7635 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1355 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2269 AN: 5178

South Asian (SAS) AF: 0.643 AC: 3105 AN: 4830

European-Finnish (FIN) AF: 0.531 AC: 5620 AN: 10580

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37343 AN: 67980

Other (OTH) AF: 0.525 AC: 1109 AN: 2112

Alfa AF: 0.440 Hom.: 2097

Bravo AF: 0.573

Asia WGS AF: 0.601 AC: 2092 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Ovarian dysgenesis 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	18
DANN	Benign	0.76
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2292752; hg19: chr17-40725656; COSMIC: COSV53817339; COSMIC: COSV53817339;