Genetic Variant XG:p.Pro105Leu (chrX-2794595-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001141919.2(XG):c.314C>T(p.Pro105Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,209,718 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 68 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 5 hem., cov: 24)

Exomes 𝑓: 0.00011 ( 0 hom. 63 hem. )

Consequence

XG
NM_001141919.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0740

Publications

0 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015495092).

BS2

High Hemizygotes in GnomAd4 at 5 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.314C>T	p.Pro105Leu	missense	Exon 6 of 11	NP_001135391.1	P55808-3
XG	NM_001141920.2		c.317C>T	p.Pro106Leu	missense	Exon 6 of 10	NP_001135392.1	P55808-2
XG	NM_175569.3		c.314C>T	p.Pro105Leu	missense	Exon 6 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.314C>T	p.Pro105Leu	missense	Exon 6 of 11	ENSP00000494087.1	P55808-3
XG	ENST00000381174.10	TSL:1	c.314C>T	p.Pro105Leu	missense	Exon 6 of 10	ENSP00000370566.5	P55808-1
XG	ENST00000419513.7	TSL:1	c.248C>T	p.Pro83Leu	missense	Exon 4 of 9	ENSP00000411004.3	A0A2U3U020

Frequencies

GnomAD3 genomes

AF:

0.0000711

AC:

AN:

112533

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:

0.00218

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000168

AC:

AN:

178904

AF XY:

0.000234

show subpopulations

Gnomad AFR exome

AF:

0.0000786

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:

0.0000625

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000111

AC:

122

AN:

1097133

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

362569

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26376

American (AMR)

AF:

0.00

AC:

AN:

35115

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19361

East Asian (EAS)

AF:

0.00

AC:

AN:

30131

South Asian (SAS)

AF:

0.00124

AC:

AN:

53864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40411

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.0000594

AC:

AN:

841719

Other (OTH)

AF:

0.0000869

AC:

AN:

46024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000711

AC:

AN:

112585

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

AN XY:

34755

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31011

American (AMR)

AF:

0.00

AC:

AN:

10651

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3573

South Asian (SAS)

AF:

0.00218

AC:

AN:

2747

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000375

AC:

AN:

53308

Other (OTH)

AF:

0.00

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000142

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.000222

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

Benign

0.18

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.2

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

FATHMM_MKL

Benign

0.0089

LIST_S2

Benign

0.56

M_CAP

Benign

0.0043

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

-0.074

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.060

Sift

Benign

0.034

Sift4G

Benign

0.27

Polyphen

0.99

Vest4

0.16

MVP

0.12

MPC

0.12

ClinPred

0.089

GERP RS

1.2

Varity_R

0.045

gMVP

0.13

Mutation Taster

=99/1

polymorphism

(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

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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