chr22-27750781-G-GAAA

Variant names:

• chr22-27750781-G-GAAA
• rs377485634
• NM_002430.3:c.*131_*133dupTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002430.3(MN1):​c.*131_*133dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 497,820 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000024 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: MN1 NM_002430.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

Genes affected

MN1 (HGNC:7180): (MN1 proto-oncogene, transcriptional regulator) Meningioma 1 (MN1) contains two sets of CAG repeats. It is disrupted by a balanced translocation (4;22) in a meningioma, and its inactivation may contribute to meningioma 32 pathogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MN1	NM_002430.3	c.*131_*133dupTTT		3_prime_UTR_variant	Exon 2 of 2	ENST00000302326.5	NP_002421.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MN1	ENST00000302326	c.*131_*133dupTTT		3_prime_UTR_variant	Exon 2 of 2	1	NM_002430.3	ENSP00000304956.4

Frequencies

GnomAD3 genomes AF: 0.0000241 AC: 1 AN: 41416 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000446

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000129 AC: 59 AN: 456404 Hom.: 0 Cov.: 6 AF XY: 0.000130 AC XY: 30 AN XY: 230036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000212

Gnomad4 ASJ exome AF: 0.000194

Gnomad4 EAS exome AF: 0.000315

Gnomad4 SAS exome AF: 0.000154

Gnomad4 FIN exome AF: 0.000143

Gnomad4 NFE exome AF: 0.000117

Gnomad4 OTH exome AF: 0.0000889

GnomAD4 genome AF: 0.0000241 AC: 1 AN: 41416 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 19570

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000446

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs377485634; hg19: chr22-28146769;