chr22-42693708-GGAA-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_017436.7(A4GALT):c.241_243delTTC(p.Phe81del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000548 in 1,405,400 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Affects (no stars).
Frequency
Genomes: 𝑓 0.000049 ( 0 hom., cov: 26)
Exomes 𝑓: 0.000055 ( 0 hom. )
Consequence
A4GALT
NM_017436.7 conservative_inframe_deletion
NM_017436.7 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.30
Publications
5 publications found
Genes affected
A4GALT (HGNC:18149): (alpha 1,4-galactosyltransferase (P1PK blood group)) The protein encoded by this gene catalyzes the transfer of galactose to lactosylceramide to form globotriaosylceramide, which has been identified as the P(k) antigen of the P blood group system. This protein, a type II membrane protein found in the Golgi, is also required for the synthesis of the bacterial verotoxins receptor. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]
CYB5R3 (HGNC:2873): (cytochrome b5 reductase 3) This gene encodes cytochrome b5 reductase, which includes a membrane-bound form in somatic cells (anchored in the endoplasmic reticulum, mitochondrial and other membranes) and a soluble form in erythrocytes. The membrane-bound form exists mainly on the cytoplasmic side of the endoplasmic reticulum and functions in desaturation and elongation of fatty acids, in cholesterol biosynthesis, and in drug metabolism. The erythrocyte form is located in a soluble fraction of circulating erythrocytes and is involved in methemoglobin reduction. The membrane-bound form has both membrane-binding and catalytic domains, while the soluble form has only the catalytic domain. Alternate splicing results in multiple transcript variants. Mutations in this gene cause methemoglobinemias. [provided by RefSeq, Jan 2010]
CYB5R3 Gene-Disease associations (from GenCC):
- methemoglobinemiaInheritance: AR Classification: DEFINITIVE Submitted by: Illumina
- methemoglobinemia due to deficiency of methemoglobin reductaseInheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- hereditary methemoglobinemiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_017436.7. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| A4GALT | NM_017436.7 | c.241_243delTTC | p.Phe81del | conservative_inframe_deletion | Exon 3 of 3 | ENST00000642412.2 | NP_059132.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000488 AC: 7AN: 143482Hom.: 0 Cov.: 26 show subpopulations
GnomAD3 genomes
AF:
AC:
7
AN:
143482
Hom.:
Cov.:
26
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000399 AC: 10AN: 250810 AF XY: 0.0000368 show subpopulations
GnomAD2 exomes
AF:
AC:
10
AN:
250810
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000555 AC: 70AN: 1261918Hom.: 0 AF XY: 0.0000543 AC XY: 34AN XY: 625976 show subpopulations
GnomAD4 exome
AF:
AC:
70
AN:
1261918
Hom.:
AF XY:
AC XY:
34
AN XY:
625976
show subpopulations
African (AFR)
AF:
AC:
0
AN:
27620
American (AMR)
AF:
AC:
4
AN:
38602
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18834
East Asian (EAS)
AF:
AC:
0
AN:
23268
South Asian (SAS)
AF:
AC:
2
AN:
84300
European-Finnish (FIN)
AF:
AC:
0
AN:
34630
Middle Eastern (MID)
AF:
AC:
1
AN:
4722
European-Non Finnish (NFE)
AF:
AC:
57
AN:
982910
Other (OTH)
AF:
AC:
6
AN:
47032
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000488 AC: 7AN: 143482Hom.: 0 Cov.: 26 AF XY: 0.0000430 AC XY: 3AN XY: 69754 show subpopulations
GnomAD4 genome
AF:
AC:
7
AN:
143482
Hom.:
Cov.:
26
AF XY:
AC XY:
3
AN XY:
69754
show subpopulations
African (AFR)
AF:
AC:
1
AN:
39488
American (AMR)
AF:
AC:
3
AN:
14504
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3364
East Asian (EAS)
AF:
AC:
0
AN:
4314
South Asian (SAS)
AF:
AC:
0
AN:
3812
European-Finnish (FIN)
AF:
AC:
0
AN:
9412
Middle Eastern (MID)
AF:
AC:
0
AN:
308
European-Non Finnish (NFE)
AF:
AC:
3
AN:
65460
Other (OTH)
AF:
AC:
0
AN:
1964
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Affects
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
p phenotype Other:1
Jan 01, 2002
OMIM
Significance:Affects
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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