4-153414852-G-C

Variant names:

• chr4-153414852-G-C
• NM_032117.4:c.613G>C

Variant summary

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

The NM_032117.4(MND1):​c.613G>C​(p.Asp205His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000824 in 1,213,926 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: MND1 NM_032117.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.27

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.613G>C	p.Asp205His	missense_variant	Exon 8 of 8	ENST00000240488.8	NP_115493.1
MND1	XM_005263275.3	c.568G>C	p.Asp190His	missense_variant	Exon 7 of 7		XP_005263332.1
MND1	NM_001253861.1	c.*129G>C		3_prime_UTR_variant	Exon 7 of 7		NP_001240790.1
MND1	NR_045605.2	n.824G>C		non_coding_transcript_exon_variant	Exon 10 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MND1	ENST00000240488.8	c.613G>C	p.Asp205His	missense_variant	Exon 8 of 8	1	NM_032117.4	ENSP00000240488.3
ENSG00000288637	ENST00000675079.1	c.2704G>C	p.Asp902His	missense_variant	Exon 18 of 18			ENSP00000502677.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.24e-7 AC: 1 AN: 1213926 Hom.: 0 Cov.: 17 AF XY: 0.00000164 AC XY: 1 AN XY: 609048

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0063	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.48		Loss of stability (P = 0.1115);
MVP		0.59
MPC		0.46
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-154336004;