19-10631490-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020428.4(SLC44A2):​c.457C>T​(p.Leu153Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00516 in 1,614,060 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0053 ( 18 hom. )

Consequence

SLC44A2
NM_020428.4 missense

Scores

1
6
11

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.43
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0039951503).
BP6
Variant 19-10631490-C-T is Benign according to our data. Variant chr19-10631490-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649298.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC44A2NM_020428.4 linkc.457C>T p.Leu153Phe missense_variant Exon 7 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.457C>T p.Leu153Phe missense_variant Exon 7 of 22 1 NM_020428.4 ENSP00000336888.4 Q8IWA5-1

Frequencies

GnomAD3 genomes
AF:
0.00417
AC:
635
AN:
152138
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00113
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00452
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00700
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00430
AC:
1079
AN:
251190
Hom.:
3
AF XY:
0.00426
AC XY:
578
AN XY:
135770
show subpopulations
Gnomad AFR exome
AF:
0.00117
Gnomad AMR exome
AF:
0.00376
Gnomad ASJ exome
AF:
0.00506
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00173
Gnomad FIN exome
AF:
0.00181
Gnomad NFE exome
AF:
0.00664
Gnomad OTH exome
AF:
0.00522
GnomAD4 exome
AF:
0.00526
AC:
7695
AN:
1461804
Hom.:
18
Cov.:
38
AF XY:
0.00516
AC XY:
3750
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00119
Gnomad4 AMR exome
AF:
0.00378
Gnomad4 ASJ exome
AF:
0.00601
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00169
Gnomad4 FIN exome
AF:
0.00154
Gnomad4 NFE exome
AF:
0.00609
Gnomad4 OTH exome
AF:
0.00490
GnomAD4 genome
AF:
0.00417
AC:
635
AN:
152256
Hom.:
3
Cov.:
32
AF XY:
0.00365
AC XY:
272
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00113
Gnomad4 AMR
AF:
0.00452
Gnomad4 ASJ
AF:
0.00634
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000828
Gnomad4 FIN
AF:
0.000659
Gnomad4 NFE
AF:
0.00700
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.00483
Hom.:
1
Bravo
AF:
0.00409
TwinsUK
AF:
0.00431
AC:
16
ALSPAC
AF:
0.00597
AC:
23
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00640
AC:
55
ExAC
AF:
0.00431
AC:
523
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00731
EpiControl
AF:
0.00670

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

SLC44A2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.34
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
T;.;T;.;.
Eigen
Benign
0.096
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.71
T;T;T;T;T
MetaRNN
Benign
0.0040
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.4
.;.;M;.;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-2.5
.;N;N;.;.
REVEL
Benign
0.13
Sift
Uncertain
0.0080
.;D;D;.;.
Sift4G
Benign
0.072
T;T;T;D;T
Polyphen
0.15, 0.092
.;B;B;.;.
Vest4
0.28, 0.27, 0.28
MVP
0.47
MPC
0.46
ClinPred
0.078
T
GERP RS
4.9
Varity_R
0.17
gMVP
0.83

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: rs147820753; hg19: chr19-10742166; COSMIC: COSV100213425; COSMIC: COSV100213425; API