NM_006739.4:c.167+54C>A

Variant names:

• chr22-35400659-C-A
• NM_006739.4:c.167+54C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006739.4(MCM5):​c.167+54C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000074 in 1,351,792 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM5	NM_006739.4	c.167+54C>A		intron_variant	Intron 2 of 16	ENST00000216122.9	NP_006730.2
MCM5	XM_006724242.5	c.167+54C>A		intron_variant	Intron 2 of 17		XP_006724305.1
MCM5	XM_047441366.1	c.167+54C>A		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+54C>A		intron_variant	Intron 2 of 16	1	NM_006739.4	ENSP00000216122.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.40e-7 AC: 1 AN: 1351792 Hom.: 0 AF XY: 0.00000151 AC XY: 1 AN XY: 662434

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000138

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.51
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-35796652;