22-38555372-T-C

Position:

• chr22-38555372-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_007068.4(DMC1):​c.364A>G​(p.Thr122Ala) variant causes a missense change. 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DMC1 NM_007068.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.53

Genes affected

DMC1 (HGNC:2927): (DNA meiotic recombinase 1) This gene encodes a member of the superfamily of recombinases (also called DNA strand-exchange proteins). Recombinases are important for repairing double-strand DNA breaks during mitosis and meiosis. This protein, which is evolutionarily conserved, is reported to be essential for meiotic homologous recombination and may thus play an important role in generating diversity of genetic information. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

DMC1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898
• PP5: Variant 22-38555372-T-C is Pathogenic according to our data. Variant chr22-38555372-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 1328944.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-38555372-T-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DMC1	NM_007068.4	c.364A>G	p.Thr122Ala	missense_variant	6/14	ENST00000216024.7	NP_008999.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DMC1	ENST00000216024.7	c.364A>G	p.Thr122Ala	missense_variant	6/14	1	NM_007068.4	ENSP00000216024.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Azoospermia Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Genetics of Infertility and Preimplantation Genetic Diagnosis, Centre Hospitalier Universitaire Grenoble Alpes

Dec 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	.;T;.;T;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D
MetaSVM	Uncertain	0.45	D
MutationAssessor	Pathogenic	3.7	H;H;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.7	D;D;D;.;D
REVEL	Uncertain	0.58
Sift	Uncertain	0.015	D;D;D;.;D
Sift4G	Uncertain	0.029	D;D;.;D;.
Polyphen		0.98, 0.99	.;D;.;D;.
Vest4		0.79
MutPred		0.78		Gain of phosphorylation at S118 (P = 0.2112);Gain of phosphorylation at S118 (P = 0.2112);Gain of phosphorylation at S118 (P = 0.2112);Gain of phosphorylation at S118 (P = 0.2112);Gain of phosphorylation at S118 (P = 0.2112);
MVP		0.90
MPC		1.5
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.94
gMVP		0.93

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: chr22-38951377;