rs133425

Positions:

• chr22-35418969-C-G
• chr22-35418969-C-T

Variant summary

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

The ENST00000216122.9(MCM5):​c.1704-915C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,210 control chromosomes in the GnomAD database, including 1,275 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 0.11 (1275 hom., cov: 32)
• Consequence: MCM5 ENST00000216122.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM5	NM_006739.4	c.1704-915C>G		intron_variant		ENST00000216122.9	NP_006730.2
MCM5	XM_006724242.5	c.1704-915C>G		intron_variant			XP_006724305.1
MCM5	XM_047441366.1	c.1704-915C>G		intron_variant			XP_047297322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM5	ENST00000216122.9	c.1704-915C>G		intron_variant		1	NM_006739.4	ENSP00000216122	P1
MCM5	ENST00000382011.9	c.1575-915C>G		intron_variant		2		ENSP00000371441
MCM5	ENST00000493076.5	n.1287-915C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17270 AN: 152092 Hom.: 1255 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0741

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0778

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.114 AC: 17335 AN: 152210 Hom.: 1275 Cov.: 32 AF XY: 0.114 AC XY: 8466 AN XY: 74416

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.0741

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.0493

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0891

Gnomad4 NFE AF: 0.0778

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0314 Hom.: 21

Bravo AF: 0.113

Asia WGS AF: 0.101 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.68

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: rs133425; hg19: chr22-35814962;