Genetic Variant SLC36A2:c.*654A>G (chr5-151316163-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181776.3(SLC36A2):c.*654A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,688 control chromosomes in the GnomAD database, including 34,564 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 34477 hom., cov: 31)

Exomes 𝑓: 0.48 ( 87 hom. )

Consequence

SLC36A2
NM_181776.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.616

Publications

5 publications found

Variant links:

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]

SLC36A2 Gene-Disease associations (from GenCC):

iminoglycinuria
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen
hyperglycinuria
Inheritance: AD, SD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

SLC36A2 links:

ENSG00000297368 (HGNC:):

ENSG00000297368 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC36A2	NM_181776.3 link	c.*654A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000335244.9	NP_861441.2	Q495M3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC36A2	ENST00000335244.9 link	c.*654A>G	3_prime_UTR_variant	Exon 10 of 10	1	NM_181776.3	ENSP00000334223.4	Q495M3-1
ENSG00000297368	ENST00000747508.1 link	n.531+5611T>C	intron_variant	Intron 1 of 3
SLC36A2	ENST00000518280.5 link	n.*1577A>G	downstream_gene_variant		1		ENSP00000428453.1	E5RGH8
SLC36A2	ENST00000518617.5 link	n.*1674A>G	downstream_gene_variant		1		ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes

AF:

0.664

AC:

100825

AN:

151884

Hom.:

34433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.771

Gnomad AMI

AF:

0.797

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.665

Gnomad EAS

AF:

0.982

Gnomad SAS

AF:

0.803

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.637

GnomAD4 exome

AF:

0.484

AC:

332

AN:

686

Hom.:

Cov.:

AF XY:

0.482

AC XY:

192

AN XY:

398

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.622

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.717

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.428

AC:

227

AN:

530

Other (OTH)

AF:

0.800

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.664

AC:

100931

AN:

152002

Hom.:

34477

Cov.:

AF XY:

0.669

AC XY:

49685

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.771

AC:

31973

AN:

41466

American (AMR)

AF:

0.705

AC:

10768

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

2305

AN:

3468

East Asian (EAS)

AF:

0.982

AC:

5073

AN:

5164

South Asian (SAS)

AF:

0.802

AC:

3868

AN:

4820

European-Finnish (FIN)

AF:

0.554

AC:

5838

AN:

10530

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.571

AC:

38839

AN:

67972

Other (OTH)

AF:

0.641

AC:

1349

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1628

3256

4883

6511

8139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.606

Hom.:

104013

Bravo

AF:

0.679

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

4.8

(source)

DANN

Benign

0.46

PhyloP100

-0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over