5-151316740-CAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAA

Variant names:

• chr5-151316740-C-CAAAAA
• rs33912867
• NM_181776.3:c.*72_*76dupTTTTT

Variant summary

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

The NM_181776.3(SLC36A2):​c.*72_*76dupTTTTT 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 0.0016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0042 (12 hom.)
• 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 12 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.*72_*76dupTTTTT		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.*72_*76dupTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000334223.4	Q495M3-1
	SLC36A2	ENST00000518280.5	TSL:1	n.*995_*999dupTTTTT		non_coding_transcript_exon	Exon 9 of 9	ENSP00000428453.1	E5RGH8
	SLC36A2	ENST00000518617.5	TSL:1	n.*1092_*1096dupTTTTT		non_coding_transcript_exon	Exon 10 of 10	ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 82 AN: 50394 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000443

Gnomad AMI AF: 0.00246

Gnomad AMR AF: 0.00109

Gnomad ASJ AF: 0.00237

Gnomad EAS AF: 0.00880

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.0143

Gnomad NFE AF: 0.00174

Gnomad OTH AF: 0.00459

GnomAD4 exome AF: 0.00418 AC: 3509 AN: 840172 Hom.: 12 Cov.: 5 AF XY: 0.00440 AC XY: 1874 AN XY: 426088

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

African (AFR) AF: 0.00236 AC: 44 AN: 18634

American (AMR) AF: 0.00552 AC: 116 AN: 21002

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 70 AN: 15194

East Asian (EAS) AF: 0.0159 AC: 376 AN: 23586

South Asian (SAS) AF: 0.0104 AC: 560 AN: 53652

European-Finnish (FIN) AF: 0.00196 AC: 51 AN: 26086

Middle Eastern (MID) AF: 0.00392 AC: 10 AN: 2554

European-Non Finnish (NFE) AF: 0.00327 AC: 2104 AN: 643972

Other (OTH) AF: 0.00502 AC: 178 AN: 35492

⚠️ 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 AF: 0.00163 AC: 82 AN: 50396 Hom.: 0 Cov.: 0 AF XY: 0.00171 AC XY: 38 AN XY: 22210

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

African (AFR) AF: 0.000442 AC: 5 AN: 11312

American (AMR) AF: 0.00109 AC: 4 AN: 3664

Ashkenazi Jewish (ASJ) AF: 0.00237 AC: 4 AN: 1688

East Asian (EAS) AF: 0.00880 AC: 12 AN: 1364

South Asian (SAS) AF: 0.00 AC: 0 AN: 994

European-Finnish (FIN) AF: 0.00108 AC: 1 AN: 922

Middle Eastern (MID) AF: 0.0156 AC: 1 AN: 64

European-Non Finnish (NFE) AF: 0.00174 AC: 51 AN: 29324

Other (OTH) AF: 0.00456 AC: 3 AN: 658

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

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;