Genetic Variant NM_032117.4:c.507G>C (chr4-153409011-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_032117.4(MND1):c.507G>C(p.Trp169Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000659 in 1,365,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

MND1
NM_032117.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.98

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.838

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032117.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MND1	NM_032117.4	MANE Select	c.507G>C	p.Trp169Cys	missense	Exon 7 of 8	NP_115493.1	Q9BWT6
MND1	NM_001253861.1		c.*23G>C		3_prime_UTR	Exon 6 of 7	NP_001240790.1	A0A087WTC6
MND1	NR_045605.2		n.718G>C		non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MND1	ENST00000240488.8	TSL:1 MANE Select	c.507G>C	p.Trp169Cys	missense	Exon 7 of 8	ENSP00000240488.3	Q9BWT6
ENSG00000288637	ENST00000675838.1		c.2586G>C	p.Trp862Cys	missense	Exon 17 of 18	ENSP00000501593.1	A0A6Q8PF18
MND1	ENST00000504860.2	TSL:1	c.462G>C	p.Trp154Cys	missense	Exon 6 of 6	ENSP00000422933.1	D6R9E3

Frequencies

GnomAD3 genomes

AF:

0.0000142

AC:

AN:

140864

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000403

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000347

AC:

AN:

172716

AF XY:

0.0000313

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000660

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1224376

Hom.:

Cov.:

AF XY:

0.00000498

AC XY:

AN XY:

602900

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

25804

American (AMR)

AF:

0.00

AC:

AN:

24094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18698

East Asian (EAS)

AF:

0.000240

AC:

AN:

29142

South Asian (SAS)

AF:

0.00

AC:

AN:

45566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4804

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

987208

Other (OTH)

AF:

0.00

AC:

AN:

48336

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000151393), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.382

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000142

AC:

AN:

140940

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

68320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40084

American (AMR)

AF:

0.00

AC:

AN:

13968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3150

East Asian (EAS)

AF:

0.000404

AC:

AN:

4954

South Asian (SAS)

AF:

0.00

AC:

AN:

4260

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63030

Other (OTH)

AF:

0.00

AC:

AN:

1922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.48

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.84

MetaSVM

Uncertain

0.45

MutationAssessor

Pathogenic

3.8

PhyloP100

7.0

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-12

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.90

MutPred

0.86

Loss of MoRF binding (P = 0.0159)

MVP

0.47

MPC

0.54

ClinPred

1.0

GERP RS

5.4

Varity_R

0.96

gMVP

0.92

Mutation Taster

=42/58

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over