Variant 1-75215784-T-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.1698A>G(p.Ile566Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,454,956 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC44A5
NM_001130058.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.148

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:

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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	Protein	UniProt
SLC44A5	NM_001130058.2 linkuse as main transcript	c.1698A>G	p.Ile566Met	missense_variant	19/24	ENST00000370859.8	NP_001123530.1	Q8NCS7-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A5	ENST00000370859.8 linkuse as main transcript	c.1698A>G	p.Ile566Met	missense_variant	19/24	2	NM_001130058.2	ENSP00000359896.3		Q8NCS7-4
SLC44A5	ENST00000370855.5 linkuse as main transcript	c.1698A>G	p.Ile566Met	missense_variant	19/24	1		ENSP00000359892.5		Q8NCS7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250438

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135388

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:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1454956

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724290

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 04, 2024

The c.1698A>G (p.I566M) alteration is located in exon 19 (coding exon 18) of the SLC44A5 gene. This alteration results from a A to G substitution at nucleotide position 1698, causing the isoleucine (I) at amino acid position 566 to be replaced by a methionine (M). 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

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.052

.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.11

Sift

Benign

0.053

T;T

Sift4G

Benign

0.061

T;T

Polyphen

0.26

.;B

Vest4

0.26

MutPred

0.81

Loss of methylation at K567 (P = 0.0265);Loss of methylation at K567 (P = 0.0265);

MVP

0.15

MPC

0.75

ClinPred

0.24

GERP RS

-4.9

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