19-10631631-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020428.4(SLC44A2):​c.508C>T​(p.Arg170Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R170P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SLC44A2
NM_020428.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04
Variant links:
Genes affected
SLC44A2 (HGNC:17292): (solute carrier family 44 member 2 (CTL2 blood group)) Enables choline transmembrane transporter activity. Involved in choline transport and transmembrane transport. Located in mitochondrion and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26453874).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC44A2NM_020428.4 linkc.508C>T p.Arg170Trp missense_variant Exon 8 of 22 ENST00000335757.10 NP_065161.3 Q8IWA5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC44A2ENST00000335757.10 linkc.508C>T p.Arg170Trp missense_variant Exon 8 of 22 1 NM_020428.4 ENSP00000336888.4 Q8IWA5-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250340
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135350
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461488
Hom.:
0
Cov.:
79
AF XY:
0.00000275
AC XY:
2
AN XY:
727038
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.0000480
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.508C>T (p.R170W) alteration is located in exon 8 (coding exon 8) of the SLC44A2 gene. This alteration results from a C to T substitution at nucleotide position 508, causing the arginine (R) at amino acid position 170 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.081
T;.;T;.;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.26
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
.;.;M;.;M
PrimateAI
Benign
0.22
T
PROVEAN
Uncertain
-2.5
.;D;D;.;.
REVEL
Benign
0.11
Sift
Benign
0.035
.;D;D;.;.
Sift4G
Uncertain
0.0050
D;D;D;D;D
Polyphen
0.97, 0.95
.;D;P;.;.
Vest4
0.50, 0.49, 0.48
MutPred
0.50
.;.;Loss of catalytic residue at R170 (P = 0.0202);.;Loss of catalytic residue at R170 (P = 0.0202);
MVP
0.46
MPC
0.59
ClinPred
0.90
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.18
gMVP
0.86

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: rs971446075; hg19: chr19-10742307; API