7-20647550-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001163941.2(ABCB5):c.997A>T(p.Ile333Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000076 in 1,578,314 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000075 ( 0 hom. )
Consequence
ABCB5
NM_001163941.2 missense
NM_001163941.2 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 0.549
Genes affected
ABCB5 (HGNC:46): (ATP binding cassette subfamily B member 5) ABCB5 belongs to the ATP-binding cassette (ABC) transporter superfamily of integral membrane proteins. These proteins participate in ATP-dependent transmembrane transport of structurally diverse molecules ranging from small ions, sugars, and peptides to more complex organic molecules (Chen et al., 2005 [PubMed 15760339]).[supplied by OMIM, Mar 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCB5 | NM_001163941.2 | c.997A>T | p.Ile333Phe | missense_variant | 10/28 | ENST00000404938.7 | |
ABCB5 | NM_001163942.2 | c.-339A>T | 5_prime_UTR_variant | 1/6 | |||
ABCB5 | NM_001163993.3 | c.-339A>T | 5_prime_UTR_variant | 1/6 | |||
ABCB5 | NM_178559.6 | c.-339A>T | 5_prime_UTR_variant | 1/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCB5 | ENST00000404938.7 | c.997A>T | p.Ile333Phe | missense_variant | 10/28 | 1 | NM_001163941.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152160Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
13
AN:
152160
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000400 AC: 8AN: 199960Hom.: 0 AF XY: 0.0000653 AC XY: 7AN XY: 107184
GnomAD3 exomes
AF:
AC:
8
AN:
199960
Hom.:
AF XY:
AC XY:
7
AN XY:
107184
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000750 AC: 107AN: 1426154Hom.: 0 Cov.: 30 AF XY: 0.0000765 AC XY: 54AN XY: 706096
GnomAD4 exome
AF:
AC:
107
AN:
1426154
Hom.:
Cov.:
30
AF XY:
AC XY:
54
AN XY:
706096
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152160Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74334
GnomAD4 genome
?
AF:
AC:
13
AN:
152160
Hom.:
Cov.:
33
AF XY:
AC XY:
6
AN XY:
74334
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
1
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 submitter | clinical testing | Ambry Genetics | Nov 10, 2022 | The c.997A>T (p.I333F) alteration is located in exon 10 (coding exon 9) of the ABCB5 gene. This alteration results from a A to T substitution at nucleotide position 997, causing the isoleucine (I) at amino acid position 333 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at