Variant 9-105244890-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_080546.5(SLC44A1):c.22T>A(p.Ser8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,175,462 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. S8F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0038 ( 9 hom. )

Consequence

SLC44A1
NM_080546.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.312

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:

LOC112268038 (HGNC:):

LOC112268038 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0089713335).

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A1	NM_080546.5 linkuse as main transcript	c.22T>A	p.Ser8Thr	missense_variant	1/16	ENST00000374720.8
LOC112268038	XR_002956866.2 linkuse as main transcript	n.575+129A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A1	ENST00000374720.8 linkuse as main transcript	c.22T>A	p.Ser8Thr	missense_variant	1/16	1	NM_080546.5	P1	Q8WWI5-1

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

319

AN:

148330

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000743

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000868

Gnomad ASJ

AF:

0.00464

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000825

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00368

Gnomad OTH

AF:

0.00296

GnomAD3 exomes

AF:

0.00307

AC:

AN:

326

Hom.:

AF XY:

0.00

AC XY:

AN XY:

164

show subpopulations

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00495

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00385

AC:

3950

AN:

1027024

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

1903

AN XY:

484884

show subpopulations

Gnomad4 AFR exome

AF:

0.000384

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.00491

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.00423

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00215

AC:

319

AN:

148438

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

142

AN XY:

72574

show subpopulations

Gnomad4 AFR

AF:

0.000741

Gnomad4 AMR

AF:

0.000867

Gnomad4 ASJ

AF:

0.00464

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000825

Gnomad4 NFE

AF:

0.00368

Gnomad4 OTH

AF:

0.00293

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00219

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

Aug 02, 2021

The c.22T>A (p.S8T) alteration is located in exon 1 (coding exon 1) of the SLC44A1 gene. This alteration results from a T to A substitution at nucleotide position 22, causing the serine (S) at amino acid position 8 to be replaced by a threonine (T). 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

0.072

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.60

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.38

T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0090

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.94

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.69

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.065

B;B;.

Vest4

0.092

MVP

0.20

MPC

0.30

ClinPred

0.063

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.12

gMVP

0.27

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