Genetic Variant NM_053274.3:c.1452A>T (chr1-92262884-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_053274.3(GLMN):c.1452A>T(p.Lys484Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GLMN
NM_053274.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

Publications

0 publications found

Variant links:

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

GLMN links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLMN	NM_053274.3	MANE Select	c.1452A>T	p.Lys484Asn	missense	Exon 16 of 19	NP_444504.1	Q92990-1
GLMN	NM_001319683.2		c.1410A>T	p.Lys470Asn	missense	Exon 15 of 18	NP_001306612.1	B4DJ85
GLMN	NR_135089.2		n.1460A>T		non_coding_transcript_exon	Exon 15 of 18

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLMN	ENST00000370360.8	TSL:1 MANE Select	c.1452A>T	p.Lys484Asn	missense	Exon 16 of 19	ENSP00000359385.3	Q92990-1
GLMN	ENST00000495106.5	TSL:1	n.*113A>T		non_coding_transcript_exon	Exon 15 of 18	ENSP00000436829.1	Q92990-2
GLMN	ENST00000495106.5	TSL:1	n.*113A>T		3_prime_UTR	Exon 15 of 18	ENSP00000436829.1	Q92990-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1012270

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

519806

African (AFR)

AF:

0.00

AC:

AN:

25558

American (AMR)

AF:

0.00

AC:

AN:

42882

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22578

East Asian (EAS)

AF:

0.00

AC:

AN:

36828

South Asian (SAS)

AF:

0.00

AC:

AN:

77254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50654

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4808

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

707130

Other (OTH)

AF:

0.00

AC:

AN:

44578

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.1

PhyloP100

1.5

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.21

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.030

Polyphen

0.99

Vest4

0.71

MutPred

0.66

Loss of ubiquitination at K484 (P = 0.0148)

MVP

0.78

MPC

0.37

ClinPred

0.97

GERP RS

4.5

Varity_R

0.71

gMVP

0.46

Mutation Taster

=47/53

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over