rs117101952

Variant names:

• chr17-42574011-G-A
• rs117101952
• NM_016556.4:c.337+88C>T

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.337+88C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00573 in 1,572,828 control chromosomes in the GnomAD database, including 307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (30 hom., cov: 33)
  • Exomes 𝑓: 0.0057 (277 hom.)
• Consequence: PSMC3IP NM_016556.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.830
• Publications: 2 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 17-42574011-G-A is Benign according to our data. Variant chr17-42574011-G-A is described in ClinVar as Benign. ClinVar VariationId is 1237505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0613 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.337+88C>T		intron	N/A	NP_057640.1	Q9P2W1-1
	PSMC3IP	NM_013290.7		c.337+88C>T		intron	N/A	NP_037422.2
	PSMC3IP	NM_001256014.2		c.148+88C>T		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.337+88C>T		intron	N/A	ENSP00000377384.2	Q9P2W1-1
	PSMC3IP	ENST00000253789.9	TSL:1	c.337+88C>T		intron	N/A	ENSP00000253789.4	Q9P2W1-2
	PSMC3IP	ENST00000587209.5	TSL:1	c.148+88C>T		intron	N/A	ENSP00000468188.1	K7ERB6

Frequencies

GnomAD3 genomes AF: 0.00555 AC: 845 AN: 152180 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00550

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.00537

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.0131 AC: 2463 AN: 187848 AF XY: 0.0161

Gnomad AFR exome AF: 0.00638

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00134

Gnomad EAS exome AF: 0.0210

Gnomad FIN exome AF: 0.00682

Gnomad NFE exome AF: 0.000900

Gnomad OTH exome AF: 0.00732

GnomAD4 exome AF: 0.00573 AC: 8143 AN: 1420530 Hom.: 277 Cov.: 33 AF XY: 0.00754 AC XY: 5303 AN XY: 703552

African (AFR) AF: 0.00596 AC: 193 AN: 32360

American (AMR) AF: 0.00102 AC: 39 AN: 38066

Ashkenazi Jewish (ASJ) AF: 0.000788 AC: 20 AN: 25388

East Asian (EAS) AF: 0.0275 AC: 1029 AN: 37422

South Asian (SAS) AF: 0.0675 AC: 5495 AN: 81360

European-Finnish (FIN) AF: 0.00637 AC: 316 AN: 49590

Middle Eastern (MID) AF: 0.00684 AC: 39 AN: 5704

European-Non Finnish (NFE) AF: 0.000487 AC: 532 AN: 1091678

Other (OTH) AF: 0.00814 AC: 480 AN: 58962

GnomAD4 genome AF: 0.00567 AC: 864 AN: 152298 Hom.: 30 Cov.: 33 AF XY: 0.00683 AC XY: 509 AN XY: 74492

African (AFR) AF: 0.00551 AC: 229 AN: 41546

American (AMR) AF: 0.00477 AC: 73 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5192

South Asian (SAS) AF: 0.0673 AC: 325 AN: 4828

European-Finnish (FIN) AF: 0.00537 AC: 57 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000573 AC: 39 AN: 68022

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00271 Hom.: 2

Bravo AF: 0.00406

Asia WGS AF: 0.0730 AC: 252 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.83
CADD	Benign	4.2
DANN	Benign	0.53
PhyloP100		0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs117101952; hg19: chr17-40726029;