Variant 9-105348387-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080546.5(SLC44A1):c.436C>T(p.Pro146Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000439 in 1,611,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

SLC44A1
NM_080546.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

SLC44A1 (HGNC:18798): (solute carrier family 44 member 1) Enables choline transmembrane transporter activity. Involved in choline transport and transmembrane transport. Located in several cellular components, including cytosol; mitochondrion; and nucleoplasm. Implicated in high grade glioma. [provided by Alliance of Genome Resources, Apr 2022]

SLC44A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026419401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC44A1	NM_080546.5 linkuse as main transcript	c.436C>T	p.Pro146Ser	missense_variant	5/16	ENST00000374720.8	NP_536856.2	Q8WWI5-1A0A024R151

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A1	ENST00000374720.8 linkuse as main transcript	c.436C>T	p.Pro146Ser	missense_variant	5/16	1	NM_080546.5	ENSP00000363852.3		Q8WWI5-1

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000490

AC:

123

AN:

251116

Hom.:

AF XY:

0.000464

AC XY:

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000810

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000443

AC:

646

AN:

1458864

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

324

AN XY:

725884

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000490

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.000407

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000648

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000613

Hom.:

Bravo

AF:

0.000450

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.000656

EpiControl

AF:

0.00124

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

The c.436C>T (p.P146S) alteration is located in exon 5 (coding exon 5) of the SLC44A1 gene. This alteration results from a C to T substitution at nucleotide position 436, causing the proline (P) at amino acid position 146 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.017

.;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.052

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.7

L;L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.77

N;N;N

REVEL

Benign

0.29

Sift

Benign

0.80

T;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.21

MVP

0.64

MPC

0.33

ClinPred

0.022

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.81

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