Variant 17-42572959-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_198204.2(MLX):c.*1356G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00591 in 1,613,974 control chromosomes in the GnomAD database, including 323 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: 32)

Exomes 𝑓: 0.0059 ( 293 hom. )

Consequence

MLX
NM_198204.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0590

Variant links:

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 links:

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]

MLX links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-42572959-G-A is Benign according to our data. Variant chr17-42572959-G-A is described in ClinVar as [Benign]. Clinvar id is 1181471.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSMC3IP	NM_016556.4 linkuse as main transcript	c.*9C>T		3_prime_UTR_variant	8/8	ENST00000393795.8
MLX	NM_198204.2 linkuse as main transcript	c.*1356G>A		3_prime_UTR_variant	8/8	ENST00000435881.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSMC3IP	ENST00000393795.8 linkuse as main transcript	c.*9C>T		3_prime_UTR_variant	8/8	1	NM_016556.4	P1	Q9P2W1-1
MLX	ENST00000435881.7 linkuse as main transcript	c.*1356G>A		3_prime_UTR_variant	8/8	1	NM_198204.2	P1	Q9UH92-3

Frequencies

GnomAD3 genomes

AF:

0.00554

AC:

844

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00540

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00477

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0208

Gnomad SAS

AF:

0.0675

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.0124

AC:

3106

AN:

251464

Hom.:

109

AF XY:

0.0148

AC XY:

2015

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00597

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.0218

Gnomad SAS exome

AF:

0.0736

Gnomad FIN exome

AF:

0.00651

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00815

GnomAD4 exome

AF:

0.00594

AC:

8682

AN:

1461634

Hom.:

293

Cov.:

AF XY:

0.00776

AC XY:

5639

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.00583

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.0277

Gnomad4 SAS exome

AF:

0.0681

Gnomad4 FIN exome

AF:

0.00642

Gnomad4 NFE exome

AF:

0.000517

Gnomad4 OTH exome

AF:

0.00813

GnomAD4 genome

AF:

0.00566

AC:

863

AN:

152340

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00541

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0210

Gnomad4 SAS

AF:

0.0676

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00152

Hom.:

Bravo

AF:

0.00400

Asia WGS

AF:

0.0730

AC:

252

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 30, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.5

DANN

Benign

0.24

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over