Genetic Variant SLC44A2:p.Leu153Phe (chr19-10631490-C-T) – ACMG Classification: Benign (-10 pts)

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

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]

SLC44A2 links:

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
SLC44A2	NM_020428.4 link	c.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
SLC44A2	ENST00000335757.10 link	c.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.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00409

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.00431

AC:

523

Asia WGS

AF:

0.00115

AC:

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

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;T;.;.

Eigen

Benign

0.096

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

T;T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.4

.;.;M;.;M

PrimateAI

Uncertain

0.58

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over