chr22-38551830-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_007068.4(DMC1):​c.421+836G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 149,884 control chromosomes in the GnomAD database, including 20 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 0.016 (20 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=-0.98).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0155 (2328/149884) while in subpopulation NFE AF = 0.0254 (1718/67708). AF 95% confidence interval is 0.0244. There are 20 homozygotes in GnomAd4. There are 1031 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2327 AN: 149798 Hom.: 20 Cov.: 28

Gnomad AFR AF: 0.00443

Gnomad AMI AF: 0.00661

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00982

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00690

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0203

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

GnomAD4 genome AF: 0.0155 AC: 2328 AN: 149884 Hom.: 20 Cov.: 28 AF XY: 0.0141 AC XY: 1031 AN XY: 72876

African (AFR) AF: 0.00442 AC: 181 AN: 40938

American (AMR) AF: 0.0128 AC: 191 AN: 14930

Ashkenazi Jewish (ASJ) AF: 0.00982 AC: 34 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00712 AC: 34 AN: 4774

European-Finnish (FIN) AF: 0.0120 AC: 116 AN: 9672

Middle Eastern (MID) AF: 0.0245 AC: 7 AN: 286

European-Non Finnish (NFE) AF: 0.0254 AC: 1718 AN: 67708

Other (OTH) AF: 0.0196 AC: 41 AN: 2088

Alfa AF: 0.00337 Hom.: 621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.5
DANN	Benign	0.70
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

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;