rs2093045125

Variant names:

• chr17-42573019-TTCC-T
• rs2093045125
• NM_016556.4:c.600_602delGGA

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP3 PP5

The NM_016556.4(PSMC3IP):​c.600_602delGGA​(p.Glu201del) variant causes a disruptive inframe deletion, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PSMC3IP NM_016556.4 disruptive_inframe_deletion, splice_region
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.01
• Publications: 0 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]

MLX (HGNC:11645): (MAX dimerization protein MLX) The product of this gene belongs to the family of basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factors. These factors form heterodimers with Mad proteins and play a role in proliferation, determination and differentiation. This gene product may act to diversify Mad family function by its restricted association with a subset of the Mad family of transcriptional repressors, namely, Mad1 and Mad4. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_016556.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 17-42573019-TTCC-T is Pathogenic according to our data. Variant chr17-42573019-TTCC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 30741.Status of the report is no_assertion_criteria_provided, 0 stars.

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.600_602delGGA	p.Glu201del	disruptive_inframe_deletion splice_region	Exon 8 of 8	NP_057640.1	Q9P2W1-1
	MLX	NM_198204.2	MANE Select	c.*1421_*1423delCCT		3_prime_UTR	Exon 8 of 8	NP_937847.1	Q9UH92-3
	PSMC3IP	NM_013290.7		c.564_566delGGA	p.Glu189del	disruptive_inframe_deletion splice_region	Exon 8 of 8	NP_037422.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMC3IP	ENST00000393795.8	TSL:1 MANE Select	c.600_602delGGA	p.Glu201del	disruptive_inframe_deletion splice_region	Exon 8 of 8	ENSP00000377384.2	Q9P2W1-1
	PSMC3IP	ENST00000253789.9	TSL:1	c.564_566delGGA	p.Glu189del	disruptive_inframe_deletion splice_region	Exon 8 of 8	ENSP00000253789.4	Q9P2W1-2
	PSMC3IP	ENST00000587209.5	TSL:1	c.411_413delGGA	p.Glu138del	disruptive_inframe_deletion splice_region	Exon 7 of 7	ENSP00000468188.1	K7ERB6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Ovarian dysgenesis 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0
Mutation Taster		=40/60	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.41		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2093045125; hg19: chr17-40725037;