5-151316740-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

• chr5-151316740-C-CAAAA
• rs33912867
• NM_181776.3:c.*73_*76dupTTTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_181776.3(SLC36A2):​c.*73_*76dupTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0078 (27 hom., cov: 0)
  • Exomes 𝑓: 0.026 (26 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC36A2 NM_181776.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.985
• Publications: 1 publications found

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

ENSG00000297368 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 26 AR,AD,SD gene

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.*73_*76dupTTTT		3_prime_UTR	Exon 10 of 10	NP_861441.2	Q495M3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC36A2	ENST00000335244.9	TSL:1 MANE Select	c.*73_*76dupTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000334223.4	Q495M3-1
	SLC36A2	ENST00000518280.5	TSL:1	n.*996_*999dupTTTT		non_coding_transcript_exon	Exon 9 of 9	ENSP00000428453.1	E5RGH8
	SLC36A2	ENST00000518617.5	TSL:1	n.*1093_*1096dupTTTT		non_coding_transcript_exon	Exon 10 of 10	ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes AF: 0.00779 AC: 392 AN: 50342 Hom.: 27 Cov.: 0

Gnomad AFR AF: 0.00421

Gnomad AMI AF: 0.00732

Gnomad AMR AF: 0.00520

Gnomad ASJ AF: 0.00351

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0169

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00483

Gnomad OTH AF: 0.00456

GnomAD4 exome AF: 0.0260 AC: 21451 AN: 825950 Hom.: 26 Cov.: 5 AF XY: 0.0269 AC XY: 11262 AN XY: 418658

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

African (AFR) AF: 0.0157 AC: 288 AN: 18356

American (AMR) AF: 0.0300 AC: 612 AN: 20422

Ashkenazi Jewish (ASJ) AF: 0.0250 AC: 372 AN: 14882

East Asian (EAS) AF: 0.0554 AC: 1265 AN: 22842

South Asian (SAS) AF: 0.0465 AC: 2417 AN: 51984

European-Finnish (FIN) AF: 0.0164 AC: 419 AN: 25568

Middle Eastern (MID) AF: 0.0249 AC: 62 AN: 2494

European-Non Finnish (NFE) AF: 0.0236 AC: 15005 AN: 634586

Other (OTH) AF: 0.0290 AC: 1011 AN: 34816

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00783 AC: 394 AN: 50344 Hom.: 27 Cov.: 0 AF XY: 0.00852 AC XY: 189 AN XY: 22180

African (AFR) AF: 0.00420 AC: 47 AN: 11180

American (AMR) AF: 0.00520 AC: 19 AN: 3652

Ashkenazi Jewish (ASJ) AF: 0.00351 AC: 6 AN: 1708

East Asian (EAS) AF: 0.114 AC: 156 AN: 1366

South Asian (SAS) AF: 0.0171 AC: 17 AN: 996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 64

European-Non Finnish (NFE) AF: 0.00483 AC: 142 AN: 29382

Other (OTH) AF: 0.00604 AC: 4 AN: 662

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.98
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs33912867; hg19: chr5-150696301;