rs743813

Positions:

• chr22-35400659-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006739.4(MCM5):​c.167+54C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,502,800 control chromosomes in the GnomAD database, including 187,687 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 0.39 (14304 hom., cov: 32)
  • Exomes 𝑓: 0.50 (173383 hom.)
• Consequence: MCM5 NM_006739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34

Genes affected

MCM5 (HGNC:6948): (minichromosome maintenance complex component 5) The protein encoded by this gene is structurally very similar to the CDC46 protein from S. cerevisiae, a protein involved in the initiation of DNA replication. The encoded protein is a member of the MCM family of chromatin-binding proteins and can interact with at least two other members of this family. The encoded protein is upregulated in the transition from the G0 to G1/S phase of the cell cycle and may actively participate in cell cycle regulation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCM5	NM_006739.4	c.167+54C>G		intron_variant		ENST00000216122.9
MCM5	XM_006724242.5	c.167+54C>G		intron_variant
MCM5	XM_047441366.1	c.167+54C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM5	ENST00000216122.9	c.167+54C>G		intron_variant		1	NM_006739.4	P1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59219 AN: 151822 Hom.: 14302 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.497 AC: 671988 AN: 1350860 Hom.: 173383 AF XY: 0.495 AC XY: 327736 AN XY: 661974

Gnomad4 AFR exome AF: 0.0989

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.494

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.390 AC: 59232 AN: 151940 Hom.: 14304 Cov.: 32 AF XY: 0.389 AC XY: 28895 AN XY: 74226

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.411

Alfa AF: 0.452 Hom.: 2106

Bravo AF: 0.370

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs743813; hg19: chr22-35796652; COSMIC: COSV53347230;