NM_078483.4:c.421C>G

Variant names:

Variant summary

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

The NM_078483.4(SLC36A1):c.421C>G(p.Arg141Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,607,672 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

SLC36A1
NM_078483.4 missense, splice_region

Scores

Splicing: ADA: 0.002966

Clinical Significance

Uncertain significance criteria provided, single submitter U: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:

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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=0.21825352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC36A1	NM_078483.4 link	c.421C>G	p.Arg141Gly	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>G	p.Arg141Gly	missense_variant, splice_region_variant	Exon 6 of 11	1	NM_078483.4	ENSP00000243389.3	Q7Z2H8-1
SLC36A1	ENST00000521925.5 link	c.421C>G	p.Arg141Gly	missense_variant, splice_region_variant	Exon 6 of 10	1		ENSP00000430305.1	E7EW39
SLC36A1	ENST00000429484.6 link	c.421C>G	p.Arg141Gly	missense_variant, splice_region_variant	Exon 6 of 9	1		ENSP00000395640.2	Q7Z2H8-4
SLC36A1	ENST00000520701.5 link	c.421C>G	p.Arg141Gly	missense_variant, splice_region_variant	Exon 6 of 11	5		ENSP00000428140.1	Q7Z2H8-1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

151562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.000221

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000205

AC:

AN:

248922

Hom.:

AF XY:

0.000230

AC XY:

AN XY:

134532

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000468

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000211

AC:

307

AN:

1455992

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

173

AN XY:

724556

show subpopulations

Gnomad4 AFR exome

AF:

0.000272

Gnomad4 AMR exome

AF:

0.000249

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000585

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.000125

AC:

AN:

151680

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74066

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000160

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.421C>G (p.R141G) alteration is located in exon 6 (coding exon 5) of the SLC36A1 gene. This alteration results from a C to G substitution at nucleotide position 421, causing the arginine (R) at amino acid position 141 to be replaced by a glycine (G). 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

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;.;T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.070

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

.;T;T;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.96

L;L;L;L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

N;N;N;.;N

REVEL

Benign

0.081

Sift

Benign

0.27

T;T;T;.;T

Sift4G

Benign

0.29

T;T;T;T;T

Polyphen

0.047

B;.;B;.;B

Vest4

0.55

MVP

0.39

MPC

0.44

ClinPred

0.022

GERP RS

4.2

Varity_R

0.20

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0030

dbscSNV1_RF

Benign

0.054

SpliceAI score (max)

0.010

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