NM_053274.3:c.165+10A>G

Variant names:

• chr1-92297394-T-C
• rs201467961
• NM_053274.3:c.165+10A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_053274.3(GLMN):​c.165+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,610,148 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 30)
  • Exomes 𝑓: 0.0034 (26 hom.)
• Consequence: GLMN NM_053274.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.526
• Publications: 0 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=-0.67).
• BP6: Variant 1-92297394-T-C is Benign according to our data. Variant chr1-92297394-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 298148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00255 (388/152062) while in subpopulation SAS AF = 0.00934 (45/4820). AF 95% confidence interval is 0.00717. There are 3 homozygotes in GnomAd4. There are 202 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 388 AD gene.

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.165+10A>G		intron	N/A	NP_444504.1	Q92990-1
	GLMN	NM_001319683.2		c.165+10A>G		intron	N/A	NP_001306612.1	B4DJ85
	GLMN	NR_135089.2		n.258+10A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLMN	ENST00000370360.8	TSL:1 MANE Select	c.165+10A>G		intron	N/A	ENSP00000359385.3	Q92990-1
	GLMN	ENST00000495106.5	TSL:1	n.165+10A>G		intron	N/A	ENSP00000436829.1	Q92990-2
	GLMN	ENST00000931421.1		c.165+10A>G		intron	N/A	ENSP00000601480.1

Frequencies

GnomAD3 genomes AF: 0.00257 AC: 390 AN: 151946 Hom.: 3 Cov.: 30

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00459

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00933

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00296

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00297 AC: 747 AN: 251370 AF XY: 0.00359

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00304

Gnomad OTH exome AF: 0.00457

GnomAD4 exome AF: 0.00339 AC: 4942 AN: 1458086 Hom.: 26 Cov.: 29 AF XY: 0.00368 AC XY: 2671 AN XY: 725600

African (AFR) AF: 0.00186 AC: 62 AN: 33392

American (AMR) AF: 0.00136 AC: 61 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 30 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39646

South Asian (SAS) AF: 0.00925 AC: 797 AN: 86142

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53398

Middle Eastern (MID) AF: 0.0110 AC: 54 AN: 4896

European-Non Finnish (NFE) AF: 0.00334 AC: 3708 AN: 1109584

Other (OTH) AF: 0.00360 AC: 217 AN: 60200

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152062 Hom.: 3 Cov.: 30 AF XY: 0.00272 AC XY: 202 AN XY: 74344

African (AFR) AF: 0.00149 AC: 62 AN: 41546

American (AMR) AF: 0.00458 AC: 70 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00934 AC: 45 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10486

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00297 AC: 202 AN: 67958

Other (OTH) AF: 0.00237 AC: 5 AN: 2106

Alfa AF: 0.00249 Hom.: 0

Bravo AF: 0.00260

Asia WGS AF: 0.00433 AC: 16 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.67
CADD	Benign	5.4
DANN	Benign	0.84
PhyloP100		0.53
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: rs201467961; hg19: chr1-92762951;