4-153355675-G-T

Variant names:

• chr4-153355675-G-T
• rs973560602
• NM_032117.4:c.91G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_032117.4(MND1):​c.91G>T​(p.Asp31Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MND1 NM_032117.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.71
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MND1	NM_032117.4	MANE Select	c.91G>T	p.Asp31Tyr	missense	Exon 3 of 8	NP_115493.1	Q9BWT6
	MND1	NM_001253861.1		c.91G>T	p.Asp31Tyr	missense	Exon 3 of 7	NP_001240790.1	A0A087WTC6
	MND1	NR_045605.2		n.141G>T		non_coding_transcript_exon	Exon 3 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MND1	ENST00000240488.8	TSL:1 MANE Select	c.91G>T	p.Asp31Tyr	missense	Exon 3 of 8	ENSP00000240488.3	Q9BWT6
	ENSG00000288637	ENST00000675838.1		c.2170G>T	p.Asp724Tyr	missense	Exon 13 of 18	ENSP00000501593.1	A0A6Q8PF18
	MND1	ENST00000504860.2	TSL:1	c.46G>T	p.Asp16Tyr	missense	Exon 2 of 6	ENSP00000422933.1	D6R9E3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		8.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.92
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.63		Loss of disorder (P = 0.0126)
MVP		0.62
MPC		0.47
ClinPred		1.0	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.90
gMVP		0.68
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs973560602; hg19: chr4-154276827; COSMIC: COSV53655371;