5-151316740-CAAAAAAAAAAAA-CAAAAAAAAAAA

Variant names:

• chr5-151316740-CA-C
• rs33912867
• NM_181776.3:c.*76delT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_181776.3(SLC36A2):​c.*76delT 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 0.010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.076 (1 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0102 (519/50702) while in subpopulation AFR AF = 0.0397 (448/11292). AF 95% confidence interval is 0.0366. There are 0 homozygotes in GnomAd4. There are 261 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

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.*76delT		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.*76delT		3_prime_UTR	Exon 10 of 10	ENSP00000334223.4	Q495M3-1
	SLC36A2	ENST00000518280.5	TSL:1	n.*999delT		non_coding_transcript_exon	Exon 9 of 9	ENSP00000428453.1	E5RGH8
	SLC36A2	ENST00000518617.5	TSL:1	n.*1096delT		non_coding_transcript_exon	Exon 10 of 10	ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 517 AN: 50700 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000726

Gnomad SAS AF: 0.00297

Gnomad FIN AF: 0.00216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00142

Gnomad OTH AF: 0.00758

GnomAD4 exome AF: 0.0759 AC: 62752 AN: 826712 Hom.: 1 Cov.: 5 AF XY: 0.0737 AC XY: 30889 AN XY: 419218

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

African (AFR) AF: 0.0638 AC: 1161 AN: 18192

American (AMR) AF: 0.0435 AC: 890 AN: 20482

Ashkenazi Jewish (ASJ) AF: 0.0719 AC: 1074 AN: 14938

East Asian (EAS) AF: 0.0335 AC: 786 AN: 23430

South Asian (SAS) AF: 0.0359 AC: 1893 AN: 52682

European-Finnish (FIN) AF: 0.0712 AC: 1811 AN: 25420

Middle Eastern (MID) AF: 0.0727 AC: 183 AN: 2516

European-Non Finnish (NFE) AF: 0.0825 AC: 52338 AN: 634206

Other (OTH) AF: 0.0751 AC: 2616 AN: 34846

⚠️ 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: 0.0102 AC: 519 AN: 50702 Hom.: 0 Cov.: 0 AF XY: 0.0117 AC XY: 261 AN XY: 22326

African (AFR) AF: 0.0397 AC: 448 AN: 11292

American (AMR) AF: 0.00491 AC: 18 AN: 3666

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

East Asian (EAS) AF: 0.000726 AC: 1 AN: 1378

South Asian (SAS) AF: 0.00301 AC: 3 AN: 998

European-Finnish (FIN) AF: 0.00216 AC: 2 AN: 924

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

European-Non Finnish (NFE) AF: 0.00142 AC: 42 AN: 29590

Other (OTH) AF: 0.00753 AC: 5 AN: 664

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)		0.0		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;