NM_053274.3:c.*115G>C

Variant names:

• chr1-92246415-C-G
• rs2046620
• NM_053274.3:c.*115G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_053274.3(GLMN):​c.*115G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 638,150 control chromosomes in the GnomAD database, including 86,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18164 hom., cov: 32)
  • Exomes 𝑓: 0.51 (68042 hom.)
• Consequence: GLMN NM_053274.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0740
• Publications: 8 publications found

Genes affected

GLMN (HGNC:14373): (glomulin, FKBP associated protein) This gene encodes a phosphorylated protein that is a member of a Skp1-Cullin-F-box-like complex. The protein is essential for normal development of the vasculature and mutations in this gene have been associated with glomuvenous malformations, also called glomangiomas. Multiple splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

GLMN Gene-Disease associations (from GenCC):

• glomuvenous malformation

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-92246415-C-G is Benign according to our data. Variant chr1-92246415-C-G is described in ClinVar as Benign. ClinVar VariationId is 298125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053274.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLMN	NM_053274.3	MANE Select	c.*115G>C		3_prime_UTR	Exon 19 of 19	NP_444504.1	Q92990-1
	GLMN	NM_001319683.2		c.*115G>C		3_prime_UTR	Exon 18 of 18	NP_001306612.1	B4DJ85
	GLMN	NR_135089.2		n.1908G>C		non_coding_transcript_exon	Exon 18 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLMN	ENST00000370360.8	TSL:1 MANE Select	c.*115G>C		3_prime_UTR	Exon 19 of 19	ENSP00000359385.3	Q92990-1
	GLMN	ENST00000896609.1		c.*115G>C		3_prime_UTR	Exon 19 of 19	ENSP00000566668.1
	GLMN	ENST00000896610.1		c.*115G>C		3_prime_UTR	Exon 18 of 18	ENSP00000566669.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72133 AN: 151772 Hom.: 18153 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.507 AC: 246556 AN: 486260 Hom.: 68042 Cov.: 4 AF XY: 0.517 AC XY: 135696 AN XY: 262532

African (AFR) AF: 0.468 AC: 5902 AN: 12624

American (AMR) AF: 0.511 AC: 10408 AN: 20378

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 8093 AN: 15278

East Asian (EAS) AF: 0.961 AC: 29556 AN: 30752

South Asian (SAS) AF: 0.708 AC: 33558 AN: 47366

European-Finnish (FIN) AF: 0.365 AC: 15655 AN: 42926

Middle Eastern (MID) AF: 0.570 AC: 1154 AN: 2024

European-Non Finnish (NFE) AF: 0.446 AC: 128521 AN: 288000

Other (OTH) AF: 0.509 AC: 13709 AN: 26912

GnomAD4 genome AF: 0.475 AC: 72164 AN: 151890 Hom.: 18164 Cov.: 32 AF XY: 0.478 AC XY: 35490 AN XY: 74234

African (AFR) AF: 0.454 AC: 18801 AN: 41416

American (AMR) AF: 0.495 AC: 7548 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1888 AN: 3468

East Asian (EAS) AF: 0.964 AC: 4991 AN: 5176

South Asian (SAS) AF: 0.715 AC: 3443 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3637 AN: 10510

Middle Eastern (MID) AF: 0.524 AC: 152 AN: 290

European-Non Finnish (NFE) AF: 0.444 AC: 30135 AN: 67930

Other (OTH) AF: 0.477 AC: 1007 AN: 2112

Alfa AF: 0.449 Hom.: 1864

Bravo AF: 0.481

Asia WGS AF: 0.798 AC: 2754 AN: 3458

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Glomuvenous malformation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.50
DANN	Benign	0.53
PhyloP100		0.074
Mutation Taster		=100/0	polymorphism

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: rs2046620; hg19: chr1-92711972; COSMIC: COSV64860075; COSMIC: COSV64860075;