chr22-35400615-C-T

Variant names:

• chr22-35400615-C-T
• rs1392748416
• NM_006739.4:c.167+10C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006739.4(MCM5):​c.167+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MCM5 NM_006739.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.688
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 22-35400615-C-T is Benign according to our data. Variant chr22-35400615-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2107286.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM5	NM_006739.4	c.167+10C>T		intron_variant	Intron 2 of 16	ENST00000216122.9	NP_006730.2
MCM5	XM_006724242.5	c.167+10C>T		intron_variant	Intron 2 of 17		XP_006724305.1
MCM5	XM_047441366.1	c.167+10C>T		intron_variant	Intron 2 of 17		XP_047297322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM5	ENST00000216122.9	c.167+10C>T		intron_variant	Intron 2 of 16	1	NM_006739.4	ENSP00000216122.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441656 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715000

African (AFR) AF: 0.00 AC: 0 AN: 33008

American (AMR) AF: 0.00 AC: 0 AN: 42996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25212

East Asian (EAS) AF: 0.00 AC: 0 AN: 39246

South Asian (SAS) AF: 0.00 AC: 0 AN: 84408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5218

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1100820

Other (OTH) AF: 0.00 AC: 0 AN: 59320

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 06, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.93
PhyloP100		0.69
PromoterAI		0.034	Neutral

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: rs1392748416; hg19: chr22-35796608;