Genetic Variant SLC36A1:p.Arg141Cys (chr5-151467200-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_078483.4(SLC36A1):c.421C>T(p.Arg141Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000446 in 1,607,668 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 3 hom. )

Consequence

SLC36A1
NM_078483.4 missense, splice_region

Scores

Splicing: ADA: 0.004932

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076419413).

BP6

Variant 5-151467200-C-T is Benign according to our data. Variant chr5-151467200-C-T is described in ClinVar as [Benign]. Clinvar id is 709820.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC36A1	NM_078483.4 link	c.421C>T	p.Arg141Cys	missense_variant, splice_region_variant	Exon 6 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.421C>T	p.Arg141Cys	missense_variant, splice_region_variant	Exon 6 of 11	1	NM_078483.4	ENSP00000243389.3	Q7Z2H8-1
SLC36A1	ENST00000521925.5 link	c.421C>T	p.Arg141Cys	missense_variant, splice_region_variant	Exon 6 of 10	1		ENSP00000430305.1	E7EW39
SLC36A1	ENST00000429484.6 link	c.421C>T	p.Arg141Cys	missense_variant, splice_region_variant	Exon 6 of 9	1		ENSP00000395640.2	Q7Z2H8-4
SLC36A1	ENST00000520701.5 link	c.421C>T	p.Arg141Cys	missense_variant, splice_region_variant	Exon 6 of 11	5		ENSP00000428140.1	Q7Z2H8-1

Frequencies

GnomAD3 genomes

AF:

0.00249

AC:

378

AN:

151560

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00876

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000657

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:

0.0000441

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000719

AC:

179

AN:

248922

Hom.:

AF XY:

0.000505

AC XY:

AN XY:

134532

show subpopulations

Gnomad AFR exome

AF:

0.00987

Gnomad AMR exome

AF:

0.000410

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000234

AC:

340

AN:

1455990

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

138

AN XY:

724554

show subpopulations

Gnomad4 AFR exome

AF:

0.00809

Gnomad4 AMR exome

AF:

0.000385

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000582

GnomAD4 genome

AF:

0.00249

AC:

377

AN:

151678

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

176

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.00871

Gnomad4 AMR

AF:

0.000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000236

Hom.:

Bravo

AF:

0.00285

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000898

AC:

109

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;.;T;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.042

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.45

.;T;T;T;T

MetaRNN

Benign

0.0076

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

L;L;L;L;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.0

N;N;N;.;N

REVEL

Benign

0.073

Sift

Benign

0.16

T;T;T;.;T

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.0040

B;.;B;.;B

Vest4

0.47

MVP

0.41

MPC

0.40

ClinPred

0.016

GERP RS

4.2

Varity_R

0.13

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0049

dbscSNV1_RF

Benign

0.026

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