chr5-151316740-CAA-C

Variant names:

• chr5-151316740-CAA-C
• rs33912867
• NM_181776.3:c.*75_*76delTT

Variant summary

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

The NM_181776.3(SLC36A2):​c.*75_*76delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 877,234 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 0.000059 (0 hom., cov: 0)
  • Exomes 𝑓: 0.022 (0 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: 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.*75_*76delTT		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.*75_*76delTT		3_prime_UTR	Exon 10 of 10	ENSP00000334223.4	Q495M3-1
	SLC36A2	ENST00000518280.5	TSL:1	n.*998_*999delTT		non_coding_transcript_exon	Exon 9 of 9	ENSP00000428453.1	E5RGH8
	SLC36A2	ENST00000518617.5	TSL:1	n.*1095_*1096delTT		non_coding_transcript_exon	Exon 10 of 10	ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 3 AN: 50736 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000338

Gnomad OTH AF: 0.00152

GnomAD4 exome AF: 0.0224 AC: 18475 AN: 826496 Hom.: 0 AF XY: 0.0217 AC XY: 9114 AN XY: 419046

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

African (AFR) AF: 0.0193 AC: 351 AN: 18222

American (AMR) AF: 0.0135 AC: 279 AN: 20594

Ashkenazi Jewish (ASJ) AF: 0.0240 AC: 358 AN: 14892

East Asian (EAS) AF: 0.0152 AC: 360 AN: 23630

South Asian (SAS) AF: 0.00803 AC: 428 AN: 53280

European-Finnish (FIN) AF: 0.0257 AC: 653 AN: 25428

Middle Eastern (MID) AF: 0.0215 AC: 54 AN: 2506

European-Non Finnish (NFE) AF: 0.0240 AC: 15164 AN: 633110

Other (OTH) AF: 0.0238 AC: 828 AN: 34834

⚠️ 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: 0.0000591 AC: 3 AN: 50738 Hom.: 0 Cov.: 0 AF XY: 0.0000448 AC XY: 1 AN XY: 22344

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

African (AFR) AF: 0.00 AC: 0 AN: 11324

American (AMR) AF: 0.00 AC: 0 AN: 3668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1712

East Asian (EAS) AF: 0.00 AC: 0 AN: 1378

South Asian (SAS) AF: 0.00 AC: 0 AN: 998

European-Finnish (FIN) AF: 0.00108 AC: 1 AN: 924

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

European-Non Finnish (NFE) AF: 0.0000338 AC: 1 AN: 29592

Other (OTH) AF: 0.00151 AC: 1 AN: 664

⚠️ 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
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs33912867; hg19: chr5-150696301;