5-151316740-CAAAAAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181776.3(SLC36A2):​c.*76dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (1102 hom., cov: 0)
  • Exomes 𝑓: 0.16 (87 hom.)
• Consequence: SLC36A2 NM_181776.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-151316740-C-CA is Benign according to our data. Variant chr5-151316740-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1242005.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.180 AC: 9125 AN: 50588 Hom.: 1101 Cov.: 0

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.155 AC: 127462 AN: 820606 Hom.: 87 Cov.: 5 AF XY: 0.153 AC XY: 63555 AN XY: 415934

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

African (AFR) AF: 0.116 AC: 2111 AN: 18176

American (AMR) AF: 0.105 AC: 2123 AN: 20258

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 2145 AN: 14776

East Asian (EAS) AF: 0.207 AC: 4809 AN: 23216

South Asian (SAS) AF: 0.141 AC: 7289 AN: 51820

European-Finnish (FIN) AF: 0.127 AC: 3222 AN: 25304

Middle Eastern (MID) AF: 0.143 AC: 358 AN: 2496

European-Non Finnish (NFE) AF: 0.159 AC: 100120 AN: 629928

Other (OTH) AF: 0.153 AC: 5285 AN: 34632

⚠️ 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: 0.180 AC: 9123 AN: 50590 Hom.: 1102 Cov.: 0 AF XY: 0.174 AC XY: 3879 AN XY: 22274

African (AFR) AF: 0.0882 AC: 998 AN: 11316

American (AMR) AF: 0.144 AC: 526 AN: 3664

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 436 AN: 1706

East Asian (EAS) AF: 0.418 AC: 575 AN: 1376

South Asian (SAS) AF: 0.330 AC: 327 AN: 990

European-Finnish (FIN) AF: 0.159 AC: 146 AN: 918

Middle Eastern (MID) AF: 0.141 AC: 9 AN: 64

European-Non Finnish (NFE) AF: 0.201 AC: 5912 AN: 29480

Other (OTH) AF: 0.156 AC: 103 AN: 662

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;