2-43813162-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_022436.3(ABCG5):ā€‹c.1910T>Cā€‹(p.Leu637Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,474,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

ABCG5
NM_022436.3 missense

Scores

5
12
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03
Variant links:
Genes affected
ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCG5NM_022436.3 linkuse as main transcriptc.1910T>C p.Leu637Pro missense_variant 13/13 ENST00000405322.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCG5ENST00000405322.8 linkuse as main transcriptc.1910T>C p.Leu637Pro missense_variant 13/131 NM_022436.3 P1Q9H222-1
ABCG5ENST00000486512.5 linkuse as main transcriptn.2431T>C non_coding_transcript_exon_variant 9/91
ABCG5ENST00000409962.1 linkuse as main transcriptn.2193T>C non_coding_transcript_exon_variant 9/92
ABCG5ENST00000644754.1 linkuse as main transcriptn.2294T>C non_coding_transcript_exon_variant 10/10

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152236
Hom.:
0
Cov.:
32
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
250656
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135454
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 SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
19
AN:
1322724
Hom.:
0
Cov.:
20
AF XY:
0.0000225
AC XY:
15
AN XY:
665674
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000216
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpJul 18, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Pathogenic
0.27
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.73
D;D
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.76
.;T
M_CAP
Uncertain
0.22
D
MetaRNN
Pathogenic
0.93
D;D
MetaSVM
Uncertain
0.29
D
MutationAssessor
Uncertain
2.1
M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.8
D;.
REVEL
Uncertain
0.48
Sift
Uncertain
0.0040
D;.
Sift4G
Pathogenic
0.0010
D;.
Polyphen
1.0
D;D
Vest4
0.72
MutPred
0.79
Loss of stability (P = 0.017);Loss of stability (P = 0.017);
MVP
0.90
MPC
0.48
ClinPred
0.85
D
GERP RS
5.0
Varity_R
0.88
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs745775861; hg19: chr2-44040301; API