Genetic Variant GPM6B:p.Leu179Phe (chrX-13779980-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001001995.3(GPM6B):c.535C>T(p.Leu179Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 1,183,794 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000011 ( 0 hom. 4 hem. )

Consequence

GPM6B
NM_001001995.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

Publications

0 publications found

Variant links:

Genes affected

GPM6B (HGNC:4461): (glycoprotein M6B) This gene encodes a membrane glycoprotein that belongs to the proteolipid protein family. Proteolipid protein family members are expressed in most brain regions and are thought to be involved in cellular housekeeping functions such as membrane trafficking and cell-to-cell communication. This protein may also be involved in osteoblast differentiation. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are located on chromosomes Y and 22. [provided by RefSeq, Jan 2016]

GPM6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001995.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPM6B	NM_001001995.3	MANE Select	c.535C>T	p.Leu179Phe	missense	Exon 5 of 8	NP_001001995.1	Q13491-4
GPM6B	NM_001001996.3		c.535C>T	p.Leu179Phe	missense	Exon 5 of 8	NP_001001996.1	Q13491-3
GPM6B	NM_001318729.2		c.358C>T	p.Leu120Phe	missense	Exon 4 of 7	NP_001305658.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPM6B	ENST00000316715.9	TSL:2 MANE Select	c.535C>T	p.Leu179Phe	missense	Exon 5 of 8	ENSP00000316861.4	Q13491-4
GPM6B	ENST00000355135.6	TSL:1	c.535C>T	p.Leu179Phe	missense	Exon 5 of 8	ENSP00000347258.2	Q13491-3
GPM6B	ENST00000356942.9	TSL:1	c.415C>T	p.Leu139Phe	missense	Exon 4 of 7	ENSP00000349420.5	Q13491-1

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

111993

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000487

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000225

AC:

AN:

178095

AF XY:

0.0000159

show subpopulations

Gnomad AFR exome

AF:

0.000306

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000112

AC:

AN:

1071749

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

343535

show subpopulations

African (AFR)

AF:

0.000115

AC:

AN:

26036

American (AMR)

AF:

0.00

AC:

AN:

34688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18782

East Asian (EAS)

AF:

0.00

AC:

AN:

29639

South Asian (SAS)

AF:

0.00

AC:

AN:

51023

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39971

Middle Eastern (MID)

AF:

0.000248

AC:

AN:

4028

European-Non Finnish (NFE)

AF:

0.00000851

AC:

AN:

822805

Other (OTH)

AF:

0.0000223

AC:

AN:

44777

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.000134

AC:

AN:

112045

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34221

show subpopulations

African (AFR)

AF:

0.000486

AC:

AN:

30839

American (AMR)

AF:

0.00

AC:

AN:

10617

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3573

South Asian (SAS)

AF:

0.00

AC:

AN:

2675

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53207

Other (OTH)

AF:

0.00

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000494

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.51

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.60

MetaRNN

Uncertain

0.66

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.7

PhyloP100

7.7

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.90

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

1.0

Vest4

0.56

MVP

0.69

MPC

1.8

ClinPred

0.56

GERP RS

5.4

Varity_R

0.79

gMVP

0.96

Mutation Taster

=49/51

disease causing

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over