chr5-151316740-CAAAAAA-C

Variant names:

• chr5-151316740-CAAAAAA-C
• rs33912867
• NM_181776.3:c.*71_*76delTTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_181776.3(SLC36A2):​c.*71_*76delTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 894,648 control chromosomes in the GnomAD database, including 23 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (4 hom., cov: 0)
  • Exomes 𝑓: 0.011 (19 hom.)
• Consequence: SLC36A2 NM_181776.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0189 (957/50724) while in subpopulation SAS AF = 0.0521 (52/998). AF 95% confidence interval is 0.0408. There are 4 homozygotes in GnomAd4. There are 461 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.*71_*76delTTTTTT		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.*71_*76delTTTTTT		3_prime_UTR	Exon 10 of 10	ENSP00000334223.4	Q495M3-1
	SLC36A2	ENST00000518280.5	TSL:1	n.*994_*999delTTTTTT		non_coding_transcript_exon	Exon 9 of 9	ENSP00000428453.1	E5RGH8
	SLC36A2	ENST00000518617.5	TSL:1	n.*1091_*1096delTTTTTT		non_coding_transcript_exon	Exon 10 of 10	ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 958 AN: 50722 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00770

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.00218

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.0429

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0136

GnomAD4 exome AF: 0.0115 AC: 9692 AN: 843924 Hom.: 19 AF XY: 0.0114 AC XY: 4870 AN XY: 428112

African (AFR) AF: 0.00348 AC: 65 AN: 18700

American (AMR) AF: 0.00317 AC: 67 AN: 21128

Ashkenazi Jewish (ASJ) AF: 0.0192 AC: 292 AN: 15224

East Asian (EAS) AF: 0.000375 AC: 9 AN: 24014

South Asian (SAS) AF: 0.0133 AC: 723 AN: 54290

European-Finnish (FIN) AF: 0.0245 AC: 638 AN: 26092

Middle Eastern (MID) AF: 0.0203 AC: 52 AN: 2562

European-Non Finnish (NFE) AF: 0.0116 AC: 7485 AN: 646244

Other (OTH) AF: 0.0101 AC: 361 AN: 35670

GnomAD4 genome AF: 0.0189 AC: 957 AN: 50724 Hom.: 4 Cov.: 0 AF XY: 0.0206 AC XY: 461 AN XY: 22336

African (AFR) AF: 0.00768 AC: 87 AN: 11326

American (AMR) AF: 0.0104 AC: 38 AN: 3670

Ashkenazi Jewish (ASJ) AF: 0.0374 AC: 64 AN: 1712

East Asian (EAS) AF: 0.00218 AC: 3 AN: 1378

South Asian (SAS) AF: 0.0521 AC: 52 AN: 998

European-Finnish (FIN) AF: 0.0991 AC: 92 AN: 928

Middle Eastern (MID) AF: 0.0469 AC: 3 AN: 64

European-Non Finnish (NFE) AF: 0.0206 AC: 609 AN: 29570

Other (OTH) AF: 0.0136 AC: 9 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		1.2
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;