chr22-35429464-A-T

Variant names:

• chr22-35429464-A-T
• rs8141025
• XM_006724242.5:c.2103+6123A>T

Variant summary

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

The XM_006724242.5(MCM5):​c.2103+6123A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 151,922 control chromosomes in the GnomAD database, including 2,316 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 0.10 (2316 hom., cov: 31)
• Consequence: MCM5 XM_006724242.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 3 publications found

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]

MCM5 Gene-Disease associations (from GenCC):

• Meier-Gorlin syndrome 8

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM5	XM_006724242.5	c.2103+6123A>T		intron_variant	Intron 16 of 17		XP_006724305.1
MCM5	XM_047441366.1	c.2103+6123A>T		intron_variant	Intron 16 of 17		XP_047297322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15801 AN: 151810 Hom.: 2316 Cov.: 31

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0459

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00623

Gnomad FIN AF: 0.00161

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0805

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

GnomAD4 genome AF: 0.104 AC: 15816 AN: 151922 Hom.: 2316 Cov.: 31 AF XY: 0.101 AC XY: 7468 AN XY: 74252

African (AFR) AF: 0.328 AC: 13570 AN: 41378

American (AMR) AF: 0.0458 AC: 698 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 155 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00602 AC: 29 AN: 4814

European-Finnish (FIN) AF: 0.00161 AC: 17 AN: 10546

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0168 AC: 1144 AN: 67978

Other (OTH) AF: 0.0797 AC: 168 AN: 2108

Alfa AF: 0.0670 Hom.: 184

Bravo AF: 0.118

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8141025; hg19: chr22-35825457;