rs737777

Variant names:

• chr22-35402053-G-T
• rs737777
• NM_006739.4:c.168-1154G>T

Variant summary

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

The NM_006739.4(MCM5):​c.168-1154G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 152,280 control chromosomes in the GnomAD database, including 363 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 0.060 (363 hom., cov: 32)
• Consequence: MCM5 NM_006739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006739.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM5	NM_006739.4	MANE Select	c.168-1154G>T		intron	N/A	NP_006730.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM5	ENST00000216122.9	TSL:1 MANE Select	c.168-1154G>T		intron	N/A	ENSP00000216122.3
	MCM5	ENST00000382011.9	TSL:2	c.168-1154G>T		intron	N/A	ENSP00000371441.5
	MCM5	ENST00000416905.1	TSL:3	c.263+587G>T		intron	N/A	ENSP00000393977.1

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9133 AN: 152162 Hom.: 363 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0744

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0600 AC: 9136 AN: 152280 Hom.: 363 Cov.: 32 AF XY: 0.0598 AC XY: 4449 AN XY: 74450

African (AFR) AF: 0.0261 AC: 1083 AN: 41564

American (AMR) AF: 0.0438 AC: 670 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3472

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5180

South Asian (SAS) AF: 0.0749 AC: 362 AN: 4832

European-Finnish (FIN) AF: 0.0929 AC: 984 AN: 10596

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0848 AC: 5766 AN: 68030

Other (OTH) AF: 0.0653 AC: 138 AN: 2112

Alfa AF: 0.0732 Hom.: 62

Bravo AF: 0.0535

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.76
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs737777; hg19: chr22-35798046;