Variant 4-153394326-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000240488.8(MND1):c.341G>T(p.Arg114Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000754 in 1,458,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MND1
ENST00000240488.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39

Variant links:

Genes affected

MND1 (HGNC:24839): (meiotic nuclear divisions 1) The product of the MND1 gene associates with HOP2 (MIM 608665) to form a stable heterodimeric complex that binds DNA and stimulates the recombinase activity of RAD51 (MIM 179617) and DMC1 (MIM 602721) (Chi et al., 2007 [PubMed 17639080]). Both the MND1 and HOP2 genes are indispensable for meiotic recombination.[supplied by OMIM, Mar 2008]

MND1 links:

ENSG00000288637 (HGNC:):

ENSG00000288637 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MND1	NM_032117.4 linkuse as main transcript	c.341G>T	p.Arg114Leu	missense_variant	5/8	ENST00000240488.8	NP_115493.1	Q9BWT6
MND1	NM_001253861.1 linkuse as main transcript	c.341G>T	p.Arg114Leu	missense_variant	5/7		NP_001240790.1	A0A087WTC6
MND1	XM_005263275.3 linkuse as main transcript	c.341G>T	p.Arg114Leu	missense_variant	5/7		XP_005263332.1
MND1	NR_045605.2 linkuse as main transcript	n.552G>T		non_coding_transcript_exon_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MND1	ENST00000240488.8 linkuse as main transcript	c.341G>T	p.Arg114Leu	missense_variant	5/8	1	NM_032117.4	ENSP00000240488.3		Q9BWT6
ENSG00000288637	ENST00000675079.1 linkuse as main transcript	c.2432G>T	p.Arg811Leu	missense_variant	15/18			ENSP00000502677.1		A0A6Q8PHG4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000754

AC:

AN:

1458934

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

725842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000901

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

The c.341G>T (p.R114L) alteration is located in exon 5 (coding exon 5) of the MND1 gene. This alteration results from a G to T substitution at nucleotide position 341, causing the arginine (R) at amino acid position 114 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

T;D;T;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.73

D;D;D;D

MetaSVM

Uncertain

0.043

MutationAssessor

Pathogenic

3.7

.;H;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.8

.;D;D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0020

.;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

.;D;.;.

Vest4

0.67

MutPred

0.59

Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);.;.;

MVP

0.59

MPC

0.18

ClinPred

0.99

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.68

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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