Variant 1-75213949-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001130058.2(SLC44A5):c.1843C>G(p.Leu615Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,595,460 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SLC44A5
NM_001130058.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

Variant links:

Genes affected

SLC44A5 (HGNC:28524): (solute carrier family 44 member 5) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC44A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC44A5	NM_001130058.2 linkuse as main transcript	c.1843C>G	p.Leu615Val	missense_variant	21/24	ENST00000370859.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC44A5	ENST00000370859.8 linkuse as main transcript	c.1843C>G	p.Leu615Val	missense_variant	21/24	2	NM_001130058.2	A1	Q8NCS7-4
SLC44A5	ENST00000370855.5 linkuse as main transcript	c.1843C>G	p.Leu615Val	missense_variant	21/24	1		P4	Q8NCS7-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

243836

Hom.:

AF XY:

0.0000228

AC XY:

AN XY:

131802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

1443958

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

718394

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000164

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151502

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73892

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

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

Jan 03, 2024

The c.1843C>G (p.L615V) alteration is located in exon 21 (coding exon 20) of the SLC44A5 gene. This alteration results from a C to G substitution at nucleotide position 1843, causing the leucine (L) at amino acid position 615 to be replaced by a valine (V). 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

0.20

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

2.9

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.26

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.93

.;P

Vest4

0.55

MutPred

0.74

Loss of ubiquitination at K617 (P = 0.1372);Loss of ubiquitination at K617 (P = 0.1372);

MVP

0.30

MPC

0.83

ClinPred

0.86

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.24

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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