Genetic Variant XG:p.Thr123Lys (chrX-2797355-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001141919.2(XG):c.368C>A(p.Thr123Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,206,931 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 56 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000055 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.00015 ( 0 hom. 55 hem. )

Consequence

XG
NM_001141919.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

Publications

1 publications found

Variant links:

Genes affected

XG (HGNC:12806): (Xg glycoprotein (Xg blood group)) This gene encodes the XG blood group antigen, and is located at the pseudoautosomal boundary on the short (p) arm of chromosome X. The three 5' exons reside in the pseudoautosomal region and the remaining exons within the X-specific end. A truncated copy of this gene is found on the Y chromosome at the pseudoautosomal boundary. It is transcribed, but not expected to make a Y-chromosome specific gene product. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

XG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09884307).

BS2

High Hemizygotes in GnomAdExome4 at 55 BG gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141919.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XG	NM_001141919.2	MANE Select	c.368C>A	p.Thr123Lys	missense	Exon 7 of 11	NP_001135391.1	P55808-3
XG	NM_001141920.2		c.371C>A	p.Thr124Lys	missense	Exon 7 of 10	NP_001135392.1	P55808-2
XG	NM_175569.3		c.368C>A	p.Thr123Lys	missense	Exon 7 of 10	NP_780778.1	P55808-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XG	ENST00000644266.2	MANE Select	c.368C>A	p.Thr123Lys	missense	Exon 7 of 11	ENSP00000494087.1	P55808-3
XG	ENST00000381174.10	TSL:1	c.368C>A	p.Thr123Lys	missense	Exon 7 of 10	ENSP00000370566.5	P55808-1
XG	ENST00000419513.7	TSL:1	c.302C>A	p.Thr101Lys	missense	Exon 5 of 9	ENSP00000411004.3	A0A2U3U020

Frequencies

GnomAD3 genomes

AF:

0.0000547

AC:

AN:

109765

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000114

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000493

AC:

AN:

182690

AF XY:

0.0000447

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:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

160

AN:

1097166

Hom.:

Cov.:

AF XY:

0.000152

AC XY:

AN XY:

362554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26390

American (AMR)

AF:

0.00

AC:

AN:

35174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19365

East Asian (EAS)

AF:

0.00

AC:

AN:

30155

South Asian (SAS)

AF:

0.00

AC:

AN:

54079

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.000187

AC:

157

AN:

841389

Other (OTH)

AF:

0.0000651

AC:

AN:

46053

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000547

AC:

AN:

109765

Hom.:

Cov.:

AF XY:

0.0000312

AC XY:

AN XY:

32059

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30156

American (AMR)

AF:

0.00

AC:

AN:

10192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2629

East Asian (EAS)

AF:

0.00

AC:

AN:

3460

South Asian (SAS)

AF:

0.00

AC:

AN:

2493

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5811

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.000114

AC:

AN:

52635

Other (OTH)

AF:

0.00

AC:

AN:

1473

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.585

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000682

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Benign

0.17

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.6

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.38

M_CAP

Benign

0.0052

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.4

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.095

Sift

Pathogenic

0.0

Sift4G

Benign

0.067

Polyphen

0.97

Vest4

0.38

MutPred

0.20

Gain of solvent accessibility (P = 0.007)

MVP

0.061

MPC

0.14

ClinPred

0.061

GERP RS

1.4

Varity_R

0.34

gMVP

0.22

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over