rs3094093

Variant names:

• chr6-30711851-T-A
• rs3094093
• NM_014641.3:c.2068+23A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-30711851-T-A
• chr6-30711851-T-C
• chr6-30711851-T-G

Variant summary

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

The NM_014641.3(MDC1):​c.2068+23A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,539,230 control chromosomes in the GnomAD database, including 679,468 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 0.96 (70048 hom., cov: 32)
  • Exomes 𝑓: 0.94 (609420 hom.)
• Consequence: MDC1 NM_014641.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 34 publications found

Genes affected

MDC1 (HGNC:21163): (mediator of DNA damage checkpoint 1) The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 13 repetitions of an approximately 41-amino acid sequence. The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci. [provided by RefSeq, Jul 2008]

MDC1-AS1 (HGNC:39764): (MDC1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDC1	NM_014641.3	c.2068+23A>T		intron_variant	Intron 5 of 14	ENST00000376406.8	NP_055456.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDC1	ENST00000376406.8	c.2068+23A>T		intron_variant	Intron 5 of 14	5	NM_014641.3	ENSP00000365588.3
MDC1	ENST00000417033.1	c.40+23A>T		intron_variant	Intron 1 of 4	2		ENSP00000408962.1
MDC1-AS1	ENST00000442150.1	n.128-461T>A		intron_variant	Intron 1 of 2	3
MDC1	ENST00000494654.1	n.58+23A>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145887 AN: 152192 Hom.: 69989 Cov.: 32

Gnomad AFR AF: 0.988

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.944

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.933

Gnomad OTH AF: 0.966

GnomAD2 exomes AF: 0.959 AC: 184311 AN: 192116 AF XY: 0.960

Gnomad AFR exome AF: 0.989

Gnomad AMR exome AF: 0.976

Gnomad ASJ exome AF: 0.996

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.941

Gnomad NFE exome AF: 0.936

Gnomad OTH exome AF: 0.954

GnomAD4 exome AF: 0.937 AC: 1299569 AN: 1386920 Hom.: 609420 Cov.: 48 AF XY: 0.939 AC XY: 640195 AN XY: 681630

African (AFR) AF: 0.990 AC: 30763 AN: 31068

American (AMR) AF: 0.975 AC: 33685 AN: 34554

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 21135 AN: 21260

East Asian (EAS) AF: 1.00 AC: 39039 AN: 39040

South Asian (SAS) AF: 0.999 AC: 73749 AN: 73808

European-Finnish (FIN) AF: 0.940 AC: 46618 AN: 49578

Middle Eastern (MID) AF: 0.998 AC: 5382 AN: 5394

European-Non Finnish (NFE) AF: 0.926 AC: 995145 AN: 1075098

Other (OTH) AF: 0.946 AC: 54053 AN: 57120

GnomAD4 genome AF: 0.959 AC: 146005 AN: 152310 Hom.: 70048 Cov.: 32 AF XY: 0.959 AC XY: 71461 AN XY: 74480

African (AFR) AF: 0.988 AC: 41081 AN: 41568

American (AMR) AF: 0.965 AC: 14765 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3449 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5189 AN: 5190

South Asian (SAS) AF: 0.999 AC: 4823 AN: 4826

European-Finnish (FIN) AF: 0.944 AC: 10019 AN: 10618

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.933 AC: 63441 AN: 68010

Other (OTH) AF: 0.966 AC: 2043 AN: 2114

Alfa AF: 0.945 Hom.: 41706

Bravo AF: 0.962

Asia WGS AF: 0.997 AC: 3469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.64
PhyloP100		0.32
PromoterAI		0.022	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3094093; hg19: chr6-30679628;