NM_016556.4:c.338-147T>C

Variant names:

• chr17-42573770-A-G
• rs77165871
• NM_016556.4:c.338-147T>C

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.338-147T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,497,580 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (55 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (60 hom.)
• Consequence: PSMC3IP NM_016556.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.15
• 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]

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 17-42573770-A-G is Benign according to our data. Variant chr17-42573770-A-G is described in ClinVar as Benign. ClinVar VariationId is 1235596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 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.338-147T>C		intron	N/A	NP_057640.1	Q9P2W1-1
	PSMC3IP	NM_013290.7		c.338-183T>C		intron	N/A	NP_037422.2
	PSMC3IP	NM_001256014.2		c.149-147T>C		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.338-147T>C		intron	N/A	ENSP00000377384.2	Q9P2W1-1
	PSMC3IP	ENST00000253789.9	TSL:1	c.338-183T>C		intron	N/A	ENSP00000253789.4	Q9P2W1-2
	PSMC3IP	ENST00000587209.5	TSL:1	c.149-147T>C		intron	N/A	ENSP00000468188.1	K7ERB6

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2265 AN: 152080 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00378 AC: 497 AN: 131402 AF XY: 0.00270

Gnomad AFR exome AF: 0.0556

Gnomad AMR exome AF: 0.00276

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00151 AC: 2038 AN: 1345382 Hom.: 60 Cov.: 32 AF XY: 0.00127 AC XY: 841 AN XY: 664538

African (AFR) AF: 0.0544 AC: 1631 AN: 29964

American (AMR) AF: 0.00290 AC: 95 AN: 32710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23720

East Asian (EAS) AF: 0.00 AC: 0 AN: 35864

South Asian (SAS) AF: 0.0000655 AC: 5 AN: 76288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38482

Middle Eastern (MID) AF: 0.00230 AC: 9 AN: 3906

European-Non Finnish (NFE) AF: 0.000105 AC: 110 AN: 1048408

Other (OTH) AF: 0.00335 AC: 188 AN: 56040

GnomAD4 genome AF: 0.0149 AC: 2269 AN: 152198 Hom.: 55 Cov.: 33 AF XY: 0.0141 AC XY: 1048 AN XY: 74428

African (AFR) AF: 0.0520 AC: 2159 AN: 41524

American (AMR) AF: 0.00478 AC: 73 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68000

Other (OTH) AF: 0.0119 AC: 25 AN: 2106

Alfa AF: 0.00355 Hom.: 2

Bravo AF: 0.0170

Asia WGS AF: 0.00289 AC: 10 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	-0.83
CADD	Benign	0.64
DANN	Benign	0.64
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs77165871; hg19: chr17-40725788;