4-153394326-G-T

Variant names:

• chr4-153394326-G-T
• rs747722860
• NM_032117.4:c.341G>T

Variant summary

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

The NM_032117.4(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 NM_032117.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.39

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]

ENSG00000288637 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
MND1	NM_032117.4	c.341G>T	p.Arg114Leu	missense_variant	Exon 5 of 8	ENST00000240488.8	NP_115493.1
MND1	NM_001253861.1	c.341G>T	p.Arg114Leu	missense_variant	Exon 5 of 7		NP_001240790.1
MND1	XM_005263275.3	c.341G>T	p.Arg114Leu	missense_variant	Exon 5 of 7		XP_005263332.1
MND1	NR_045605.2	n.552G>T		non_coding_transcript_exon_variant	Exon 7 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MND1	ENST00000240488.8	c.341G>T	p.Arg114Leu	missense_variant	Exon 5 of 8	1	NM_032117.4	ENSP00000240488.3
ENSG00000288637	ENST00000675079.1	c.2432G>T	p.Arg811Leu	missense_variant	Exon 15 of 18			ENSP00000502677.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1458934 Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7 AN XY: 725842

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.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	32
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	D
LIST_S2	Benign	0.84	T;D;T;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Uncertain	0.043	D
MutationAssessor	Pathogenic	3.7	.;H;.;.
PrimateAI	Uncertain	0.51	T
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	D
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

Other links and lift over

dbSNP: rs747722860; hg19: chr4-154315478;