6-118920303-C-T

Position:

• chr6-118920303-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_017696.3(MCM9):​c.703+1702G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 152,276 control chromosomes in the GnomAD database, including 59 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 0.025 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MCM9 NM_017696.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

Genes affected

MCM9 (HGNC:21484): (minichromosome maintenance 9 homologous recombination repair factor) The protein encoded by this gene is a member of the mini-chromosome maintenance (MCM) protein family that are essential for the initiation of eukaryotic genome replication. Binding of this protein to chromatin has been shown to be a pre-requisite for recruiting the MCM2-7 helicase to DNA replication origins. This protein also binds, and is a positive regulator of, the chromatin licensing and DNA replication factor 1, CDT1. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0246 (3751/152276) while in subpopulation AFR AF= 0.0369 (1536/41572). AF 95% confidence interval is 0.0354. There are 59 homozygotes in gnomad4. There are 1875 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM9	NM_017696.3	c.703+1702G>A		intron_variant		ENST00000619706.5	NP_060166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM9	ENST00000619706.5	c.703+1702G>A		intron_variant		5	NM_017696.3	ENSP00000480469	P1
MCM9	ENST00000316068.7	c.703+1702G>A		intron_variant		1		ENSP00000312870
MCM9	ENST00000316316.10	c.703+1702G>A		intron_variant		5		ENSP00000314505	P1
MCM9	ENST00000436788.2	n.2026G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.0246 AC: 3750 AN: 152158 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0191

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0246 AC: 3751 AN: 152276 Hom.: 59 Cov.: 32 AF XY: 0.0252 AC XY: 1875 AN XY: 74448

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00664

Gnomad4 FIN AF: 0.0457

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0210 Hom.: 15

Bravo AF: 0.0211

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.65

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: rs6927681; hg19: chr6-119241468;