Genetic Variant SLC36A2:c.*70_*76delTTTTTTT (chr5-151316740-CAAAAAAA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_181776.3(SLC36A2):c.*70_*76delTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 895,744 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

SLC36A2
NM_181776.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

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

SLC36A2 links:

ENSG00000297368 (HGNC:):

ENSG00000297368 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181776.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC36A2	NM_181776.3	MANE Select	c.70_76delTTTTTTT		3_prime_UTR	Exon 10 of 10	NP_861441.2	Q495M3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC36A2	ENST00000335244.9	TSL:1 MANE Select	c.70_76delTTTTTTT	3_prime_UTR	Exon 10 of 10	ENSP00000334223.4	Q495M3-1
SLC36A2	ENST00000518280.5	TSL:1	n.993_999delTTTTTTT	non_coding_transcript_exon	Exon 9 of 9	ENSP00000428453.1	E5RGH8
SLC36A2	ENST00000518617.5	TSL:1	n.1090_1096delTTTTTTT	non_coding_transcript_exon	Exon 10 of 10	ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

50736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00136

Gnomad ASJ

AF:

0.00175

Gnomad EAS

AF:

0.000726

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000237

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00112

AC:

947

AN:

845006

Hom.:

AF XY:

0.00120

AC XY:

516

AN XY:

428726

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000321

AC:

AN:

18718

American (AMR)

AF:

0.000425

AC:

AN:

21156

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

15278

East Asian (EAS)

AF:

0.0000833

AC:

AN:

24012

South Asian (SAS)

AF:

0.00118

AC:

AN:

54460

European-Finnish (FIN)

AF:

0.00272

AC:

AN:

26148

Middle Eastern (MID)

AF:

0.00272

AC:

AN:

2570

European-Non Finnish (NFE)

AF:

0.00104

AC:

676

AN:

646924

Other (OTH)

AF:

0.00129

AC:

AN:

35740

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.349

Heterozygous variant carriers

107

160

214

267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000414

AC:

AN:

50738

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

22342

show subpopulations

African (AFR)

AF:

0.000353

AC:

AN:

11324

American (AMR)

AF:

0.00136

AC:

AN:

3670

Ashkenazi Jewish (ASJ)

AF:

0.00175

AC:

AN:

1712

East Asian (EAS)

AF:

0.000726

AC:

AN:

1378

South Asian (SAS)

AF:

0.00

AC:

AN:

998

European-Finnish (FIN)

AF:

0.00108

AC:

AN:

922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000237

AC:

AN:

29592

Other (OTH)

AF:

0.00

AC:

AN:

664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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5-151316740-CAAAAAAAAAAAA-CAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over