Variant 17-81246326-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_001037984.3(SLC38A10):c.2590G>A(p.Ala864Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,609,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SLC38A10
NM_001037984.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.226

Variant links:

Genes affected

SLC38A10 (HGNC:28237): (solute carrier family 38 member 10) Predicted to enable amino acid transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport. Predicted to act upstream of or within bone development. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

SLC38A10 links:

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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=0.06398919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A10	NM_001037984.3 link	c.2590G>A	p.Ala864Thr	missense_variant	16/16	ENST00000374759.8	NP_001033073.1	Q9HBR0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC38A10	ENST00000374759.8 link	c.2590G>A	p.Ala864Thr	missense_variant	16/16	5	NM_001037984.3	ENSP00000363891.3	Q9HBR0-1
SLC38A10	ENST00000539643.1 link	n.752-86G>A		intron_variant		1
SLC38A10	ENST00000540966.5 link	c.748G>A	p.Ala250Thr	missense_variant	5/5	3		ENSP00000437601.1	H0YF92
SLC38A10	ENST00000576151.1 link	c.718G>A	p.Ala240Thr	missense_variant	4/4	2		ENSP00000458273.1	I3L0Q8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

241938

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1456862

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

724866

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000333

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 01, 2021

The c.2590G>A (p.A864T) alteration is located in exon 16 (coding exon 16) of the SLC38A10 gene. This alteration results from a G to A substitution at nucleotide position 2590, causing the alanine (A) at amino acid position 864 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

0.077

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0061

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.97

N;N

REVEL

Benign

0.063

Sift

Benign

0.17

T;T

Sift4G

Benign

0.22

T;.

Polyphen

0.41

B;.

Vest4

0.024

MutPred

0.32

Gain of phosphorylation at A864 (P = 0.0015);.;

MVP

0.15

MPC

0.12

ClinPred

0.17

GERP RS

-1.9

Varity_R

0.064

gMVP

0.24

Splicing

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