Genetic Variant SLC36A1:p.His93Tyr (chr5-151464556-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_078483.4(SLC36A1):c.277C>T(p.His93Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC36A1
NM_078483.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC36A1	NM_078483.4 link	c.277C>T	p.His93Tyr	missense_variant	Exon 4 of 11	ENST00000243389.8	NP_510968.2	Q7Z2H8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC36A1	ENST00000243389.8 link	c.277C>T	p.His93Tyr	missense_variant	Exon 4 of 11	1	NM_078483.4	ENSP00000243389.3		Q7Z2H8-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251320

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135822

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727222

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74464

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.277C>T (p.H93Y) alteration is located in exon 4 (coding exon 3) of the SLC36A1 gene. This alteration results from a C to T substitution at nucleotide position 277, causing the histidine (H) at amino acid position 93 to be replaced by a tyrosine (Y). 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

Uncertain

0.37

BayesDel_addAF

Benign

0.0027

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T;.;T;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

1.0

D;.;D;D;D;D

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.64

D;D;D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;L;L;L;.

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-5.6

D;D;D;D;.;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;T;D;T;.;T

Sift4G

Uncertain

0.034

D;T;D;T;T;T

Polyphen

1.0, 0.99

.;D;.;D;.;D

Vest4

0.85, 0.85, 0.85

MutPred

0.69

Loss of catalytic residue at M95 (P = 0.239);Loss of catalytic residue at M95 (P = 0.239);Loss of catalytic residue at M95 (P = 0.239);Loss of catalytic residue at M95 (P = 0.239);Loss of catalytic residue at M95 (P = 0.239);Loss of catalytic residue at M95 (P = 0.239);

MVP

0.41

MPC

0.88

ClinPred

0.92

GERP RS

5.4

Varity_R

0.78

gMVP

0.89

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