5-151316740-C-CAAA

Variant names:

• chr5-151316740-C-CAAA
• rs33912867
• NM_181776.3:c.*74_*76dupTTT

Variant summary

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

The NM_181776.3(SLC36A2):​c.*74_*76dupTTT 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 0.24 (1709 hom., cov: 0)
  • Exomes 𝑓: 0.10 (124 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-CAAA is Benign according to our data. Variant chr5-151316740-C-CAAA is described in ClinVar as Benign. ClinVar VariationId is 1179293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 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.*74_*76dupTTT		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.*74_*76dupTTT		3_prime_UTR	Exon 10 of 10	ENSP00000334223.4	Q495M3-1
	SLC36A2	ENST00000518280.5	TSL:1	n.*997_*999dupTTT		non_coding_transcript_exon	Exon 9 of 9	ENSP00000428453.1	E5RGH8
	SLC36A2	ENST00000518617.5	TSL:1	n.*1094_*1096dupTTT		non_coding_transcript_exon	Exon 10 of 10	ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes AF: 0.244 AC: 12249 AN: 50278 Hom.: 1709 Cov.: 0

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.243

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.103 AC: 82658 AN: 799822 Hom.: 124 Cov.: 5 AF XY: 0.103 AC XY: 41620 AN XY: 404784

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

African (AFR) AF: 0.0799 AC: 1404 AN: 17574

American (AMR) AF: 0.101 AC: 1967 AN: 19550

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 1310 AN: 14346

East Asian (EAS) AF: 0.119 AC: 2647 AN: 22280

South Asian (SAS) AF: 0.109 AC: 5406 AN: 49756

European-Finnish (FIN) AF: 0.0659 AC: 1629 AN: 24710

Middle Eastern (MID) AF: 0.107 AC: 261 AN: 2438

European-Non Finnish (NFE) AF: 0.105 AC: 64363 AN: 615460

Other (OTH) AF: 0.109 AC: 3671 AN: 33708

⚠️ 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: 0.244 AC: 12247 AN: 50280 Hom.: 1709 Cov.: 0 AF XY: 0.236 AC XY: 5213 AN XY: 22126

African (AFR) AF: 0.123 AC: 1389 AN: 11256

American (AMR) AF: 0.246 AC: 897 AN: 3644

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 501 AN: 1698

East Asian (EAS) AF: 0.251 AC: 340 AN: 1356

South Asian (SAS) AF: 0.254 AC: 251 AN: 990

European-Finnish (FIN) AF: 0.107 AC: 97 AN: 906

Middle Eastern (MID) AF: 0.250 AC: 16 AN: 64

European-Non Finnish (NFE) AF: 0.288 AC: 8448 AN: 29304

Other (OTH) AF: 0.231 AC: 150 AN: 650

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 (auto)

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;