chr5-151316740-C-CAA

Variant names:

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

Variant summary

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

The NM_181776.3(SLC36A2):​c.*75_*76dupTT 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 (1288 hom., cov: 0)
  • Exomes 𝑓: 0.11 (91 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-CAA is Benign according to our data. Variant chr5-151316740-C-CAA is described in ClinVar as Benign. ClinVar VariationId is 1244915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 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.*75_*76dupTT		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_*76dupTT		3_prime_UTR	Exon 10 of 10	ENSP00000334223.4	Q495M3-1
	SLC36A2	ENST00000518280.5	TSL:1	n.*998_*999dupTT		non_coding_transcript_exon	Exon 9 of 9	ENSP00000428453.1	E5RGH8
	SLC36A2	ENST00000518617.5	TSL:1	n.*1095_*1096dupTT		non_coding_transcript_exon	Exon 10 of 10	ENSP00000430149.1	E5RGH8

Frequencies

GnomAD3 genomes AF: 0.180 AC: 8995 AN: 50094 Hom.: 1285 Cov.: 0

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.147

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.112 AC: 89885 AN: 803216 Hom.: 91 Cov.: 5 AF XY: 0.111 AC XY: 45015 AN XY: 407072

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

African (AFR) AF: 0.174 AC: 2996 AN: 17220

American (AMR) AF: 0.131 AC: 2578 AN: 19652

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 1418 AN: 14478

East Asian (EAS) AF: 0.141 AC: 3190 AN: 22704

South Asian (SAS) AF: 0.111 AC: 5605 AN: 50406

European-Finnish (FIN) AF: 0.0870 AC: 2147 AN: 24668

Middle Eastern (MID) AF: 0.109 AC: 261 AN: 2404

European-Non Finnish (NFE) AF: 0.110 AC: 67742 AN: 617974

Other (OTH) AF: 0.117 AC: 3948 AN: 33710

⚠️ 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: 9005 AN: 50096 Hom.: 1288 Cov.: 0 AF XY: 0.182 AC XY: 4012 AN XY: 22086

African (AFR) AF: 0.353 AC: 3980 AN: 11282

American (AMR) AF: 0.231 AC: 845 AN: 3652

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 168 AN: 1674

East Asian (EAS) AF: 0.130 AC: 178 AN: 1368

South Asian (SAS) AF: 0.113 AC: 112 AN: 994

European-Finnish (FIN) AF: 0.102 AC: 94 AN: 922

Middle Eastern (MID) AF: 0.156 AC: 10 AN: 64

European-Non Finnish (NFE) AF: 0.118 AC: 3426 AN: 29074

Other (OTH) AF: 0.181 AC: 119 AN: 658

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs33912867; hg19: chr5-150696301;