5-151316935-G-A

Position:

• chr5-151316935-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181776.3(SLC36A2):​c.1334C>T​(p.Ala445Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.043 in 1,613,876 control chromosomes in the GnomAD database, including 2,136 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.072 (613 hom., cov: 31)
  • Exomes 𝑓: 0.040 (1523 hom.)
• Consequence: SLC36A2 NM_181776.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.46

Genes affected

SLC36A2 (HGNC:18762): (solute carrier family 36 member 2) This gene encodes a pH-dependent proton-coupled amino acid transporter that belongs to the amino acid auxin permease 1 protein family. The encoded protein primarily transports small amino acids such as glycine, alanine and proline. Mutations in this gene are associated with iminoglycinuria and hyperglycinuria. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013549924).
• BP6: Variant 5-151316935-G-A is Benign according to our data. Variant chr5-151316935-G-A is described in ClinVar as [Benign]. Clinvar id is 1257807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC36A2	NM_181776.3	c.1334C>T	p.Ala445Val	missense_variant	10/10	ENST00000335244.9	NP_861441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC36A2	ENST00000335244.9	c.1334C>T	p.Ala445Val	missense_variant	10/10	1	NM_181776.3	ENSP00000334223.4

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10872 AN: 151912 Hom.: 609 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0542

GnomAD3 exomes AF: 0.0410 AC: 10299 AN: 251412 Hom.: 366 AF XY: 0.0396 AC XY: 5375 AN XY: 135894

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.0221

Gnomad ASJ exome AF: 0.0208

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0313

Gnomad FIN exome AF: 0.0607

Gnomad NFE exome AF: 0.0371

Gnomad OTH exome AF: 0.0376

GnomAD4 exome AF: 0.0401 AC: 58556 AN: 1461846 Hom.: 1523 Cov.: 80 AF XY: 0.0397 AC XY: 28861 AN XY: 727216

Gnomad4 AFR exome AF: 0.160

Gnomad4 AMR exome AF: 0.0244

Gnomad4 ASJ exome AF: 0.0191

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0324

Gnomad4 FIN exome AF: 0.0605

Gnomad4 NFE exome AF: 0.0386

Gnomad4 OTH exome AF: 0.0415

GnomAD4 genome AF: 0.0717 AC: 10894 AN: 152030 Hom.: 613 Cov.: 31 AF XY: 0.0709 AC XY: 5267 AN XY: 74320

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0418

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0322

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.0380

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0486 Hom.: 143

Bravo AF: 0.0730

TwinsUK AF: 0.0423 AC: 157

ALSPAC AF: 0.0426 AC: 164

ESP6500AA AF: 0.159 AC: 700

ESP6500EA AF: 0.0391 AC: 336

ExAC AF: 0.0442 AC: 5364

Asia WGS AF: 0.0210 AC: 74 AN: 3478

EpiCase AF: 0.0340

EpiControl AF: 0.0337

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

SLC36A2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.78
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.33	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.090
Sift	Benign	0.49	T
Sift4G	Benign	0.83	T
Polyphen		0.0	B
Vest4		0.0070
MPC		0.13
ClinPred		0.0021	T
GERP RS		-0.91
Varity_R		0.040
gMVP		0.15

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

Other links and lift over

dbSNP: rs10042608; hg19: chr5-150696496; COSMIC: COSV58864669; COSMIC: COSV58864669;