Genetic Variant NM_053274.3:c.1474-7T>C (chr1-92247996-A-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS2_Supporting

The NM_053274.3(GLMN):c.1474-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000007 in 857,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

GLMN
NM_053274.3 splice_region, intron

Scores

Splicing: ADA: 0.002692

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BS2

High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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	Effect	Exon Rank	Protein	UniProt
GLMN	NM_053274.3	MANE Select	c.1474-7T>C	splice_region intron	N/A	NP_444504.1	Q92990-1
GLMN	NM_001319683.2		c.1432-7T>C	splice_region intron	N/A	NP_001306612.1	B4DJ85
GLMN	NR_135089.2		n.1482-7T>C	splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLMN	ENST00000370360.8	TSL:1 MANE Select	c.1474-7T>C	splice_region intron	N/A	ENSP00000359385.3	Q92990-1
GLMN	ENST00000495106.5	TSL:1	n.*135-7T>C	splice_region intron	N/A	ENSP00000436829.1	Q92990-2
GLMN	ENST00000931421.1		c.1540-7T>C	splice_region intron	N/A	ENSP00000601480.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247810

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000700

AC:

AN:

857550

Hom.:

Cov.:

AF XY:

0.00000442

AC XY:

AN XY:

452144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22094

American (AMR)

AF:

0.00

AC:

AN:

43876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22348

East Asian (EAS)

AF:

0.00

AC:

AN:

36892

South Asian (SAS)

AF:

0.00

AC:

AN:

74014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49980

Middle Eastern (MID)

AF:

0.000433

AC:

AN:

4618

European-Non Finnish (NFE)

AF:

0.00000710

AC:

AN:

563212

Other (OTH)

AF:

0.00

AC:

AN:

40516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glomuvenous malformation (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0027

dbscSNV1_RF

Benign

0.066

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over