rs74315453

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017436.7(A4GALT):​c.548T>A​(p.Met183Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000226 in 1,460,960 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Affects (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

A4GALT
NM_017436.7 missense

Scores

3
14
2

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 6.31
Variant links:
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]

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 Protein UniProt
A4GALTNM_017436.7 linkuse as main transcriptc.548T>A p.Met183Lys missense_variant 3/3 ENST00000642412.2 NP_059132.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
A4GALTENST00000642412.2 linkuse as main transcriptc.548T>A p.Met183Lys missense_variant 3/3 NM_017436.7 ENSP00000494127 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000479
AC:
12
AN:
250726
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135804
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:
0.00
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.0000795
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000226
AC:
33
AN:
1460960
Hom.:
0
Cov.:
67
AF XY:
0.0000193
AC XY:
14
AN XY:
726804
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:
0.00
Gnomad4 FIN exome
AF:
0.0000759
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.0000906
AC:
11

ClinVar

Significance: Affects
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

p phenotype Other:1
Affects, no assertion criteria providedliterature onlyOMIMJun 02, 2000- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.88
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.31
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.47
T;T;T;T
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.28
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.57
.;.;T;.
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.63
D;D;D;D
MetaSVM
Uncertain
0.041
D
MutationAssessor
Uncertain
2.5
M;M;M;M
MutationTaster
Benign
0.92
A;A;A
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-4.3
.;D;D;D
REVEL
Uncertain
0.62
Sift
Uncertain
0.0030
.;D;D;D
Sift4G
Uncertain
0.0080
.;D;D;D
Polyphen
0.30
B;B;B;B
Vest4
0.93, 0.92
MVP
0.88
MPC
1.2
ClinPred
0.63
D
GERP RS
5.3
Varity_R
0.89
gMVP
0.96

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

LitVar

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

Other links and lift over

dbSNP: rs74315453; hg19: chr22-43089410; API