Genetic Variant SLC36A1:p.Ser194Leu (chr5-151467783-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_078483.4(SLC36A1):c.581C>T(p.Ser194Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SLC36A1
NM_078483.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

Variant links:

Genes affected

SLC36A1 (HGNC:18761): (solute carrier family 36 member 1) This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

SLC36A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1596545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC36A1	NM_078483.4 link	c.581C>T	p.Ser194Leu	missense_variant	Exon 7 of 11	ENST00000243389.8	NP_510968.2	Q7Z2H8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC36A1	ENST00000243389.8 link	c.581C>T	p.Ser194Leu	missense_variant	Exon 7 of 11	1	NM_078483.4	ENSP00000243389.3	Q7Z2H8-1
SLC36A1	ENST00000521925.5 link	c.581C>T	p.Ser194Leu	missense_variant	Exon 7 of 10	1		ENSP00000430305.1	E7EW39
SLC36A1	ENST00000429484.6 link	c.581C>T	p.Ser194Leu	missense_variant	Exon 7 of 9	1		ENSP00000395640.2	Q7Z2H8-4
SLC36A1	ENST00000520701.5 link	c.581C>T	p.Ser194Leu	missense_variant	Exon 7 of 11	5		ENSP00000428140.1	Q7Z2H8-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000775

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:

0.0000676

AC:

AN:

251488

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000924

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000777

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.581C>T (p.S194L) alteration is located in exon 7 (coding exon 6) of the SLC36A1 gene. This alteration results from a C to T substitution at nucleotide position 581, causing the serine (S) at amino acid position 194 to be replaced by a leucine (L). 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

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

T;.;T;.;.

Eigen

Benign

-0.082

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

.;D;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.1

L;L;L;L;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.070

N;N;N;.;N

REVEL

Benign

0.25

Sift

Benign

0.59

T;T;T;.;T

Sift4G

Benign

0.35

T;T;T;T;T

Polyphen

0.46

P;.;P;.;B

Vest4

0.83

MutPred

0.54

Loss of catalytic residue at S194 (P = 0.096);Loss of catalytic residue at S194 (P = 0.096);Loss of catalytic residue at S194 (P = 0.096);Loss of catalytic residue at S194 (P = 0.096);Loss of catalytic residue at S194 (P = 0.096);

MVP

0.32

MPC

0.37

ClinPred

0.099

GERP RS

4.8

Varity_R

0.17

gMVP

0.80

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