22-38551830-C-T

Variant names:

• chr22-38551830-C-T
• rs5757133
• NM_007068.4:c.421+836G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007068.4(DMC1):​c.421+836G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 149,770 control chromosomes in the GnomAD database, including 5,066 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5066 hom., cov: 28)
• Consequence: DMC1 NM_007068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMC1	NM_007068.4	c.421+836G>A		intron_variant	Intron 7 of 13	ENST00000216024.7	NP_008999.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMC1	ENST00000216024.7	c.421+836G>A		intron_variant	Intron 7 of 13	1	NM_007068.4	ENSP00000216024.2
DMC1	ENST00000428462.6	c.421+836G>A		intron_variant	Intron 6 of 10	2		ENSP00000412703.2
DMC1	ENST00000439567.5	c.421+836G>A		intron_variant	Intron 7 of 8	3		ENSP00000391385.1
DMC1	ENST00000478820.1	n.596+836G>A		intron_variant	Intron 7 of 7	2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 36478 AN: 149684 Hom.: 5064 Cov.: 28

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.317

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.253

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 36488 AN: 149770 Hom.: 5066 Cov.: 28 AF XY: 0.245 AC XY: 17822 AN XY: 72820

African (AFR) AF: 0.113 AC: 4605 AN: 40914

American (AMR) AF: 0.216 AC: 3219 AN: 14912

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3464

East Asian (EAS) AF: 0.360 AC: 1837 AN: 5108

South Asian (SAS) AF: 0.281 AC: 1341 AN: 4768

European-Finnish (FIN) AF: 0.332 AC: 3203 AN: 9658

Middle Eastern (MID) AF: 0.325 AC: 93 AN: 286

European-Non Finnish (NFE) AF: 0.300 AC: 20269 AN: 67670

Other (OTH) AF: 0.257 AC: 536 AN: 2082

Alfa AF: 0.187 Hom.: 621

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.79
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5757133; hg19: chr22-38947835; COSMIC: COSV53258795; COSMIC: COSV53258795;