Variant 6-30700597-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_014641.3(MDC1):c.6138C>T(p.Phe2046=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 1,612,902 control chromosomes in the GnomAD database, including 690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.041 ( 298 hom., cov: 31)

Exomes 𝑓: 0.013 ( 392 hom. )

Consequence

MDC1
NM_014641.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.676

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 6-30700597-G-A is Benign according to our data. Variant chr6-30700597-G-A is described in ClinVar as [Benign]. Clinvar id is 1265487.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.676 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDC1	NM_014641.3 linkuse as main transcript	c.6138C>T	p.Phe2046=	synonymous_variant	15/15	ENST00000376406.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDC1	ENST00000376406.8 linkuse as main transcript	c.6138C>T	p.Phe2046=	synonymous_variant	15/15	5	NM_014641.3	P1	Q14676-1
MDC1	ENST00000489540.1 linkuse as main transcript	n.1120C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

6229

AN:

152052

Hom.:

299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0356

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.0177

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00903

Gnomad OTH

AF:

0.0464

GnomAD3 exomes

AF:

0.0200

AC:

4927

AN:

245976

Hom.:

147

AF XY:

0.0180

AC XY:

2414

AN XY:

134172

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.0260

Gnomad ASJ exome

AF:

0.0509

Gnomad EAS exome

AF:

0.0144

Gnomad SAS exome

AF:

0.00458

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0234

GnomAD4 exome

AF:

0.0132

AC:

19258

AN:

1460732

Hom.:

392

Cov.:

AF XY:

0.0126

AC XY:

9143

AN XY:

726686

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.0277

Gnomad4 ASJ exome

AF:

0.0487

Gnomad4 EAS exome

AF:

0.0351

Gnomad4 SAS exome

AF:

0.00408

Gnomad4 FIN exome

AF:

0.00162

Gnomad4 NFE exome

AF:

0.00859

Gnomad4 OTH exome

AF:

0.0193

GnomAD4 genome

AF:

0.0410

AC:

6237

AN:

152170

Hom.:

298

Cov.:

AF XY:

0.0395

AC XY:

2939

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.0356

Gnomad4 ASJ

AF:

0.0412

Gnomad4 EAS

AF:

0.0177

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00903

Gnomad4 OTH

AF:

0.0459

Alfa

AF:

0.0250

Hom.:

Bravo

AF:

0.0485

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0135

EpiControl

AF:

0.0133

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 14, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.4

DANN

Benign

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over