chr5-151467262-T-TCTGG

Variant names:

• chr5-151467262-T-TCTGG
• rs755546492
• NM_078483.4:c.487_490dupGCTG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_078483.4(SLC36A1):​c.487_490dupGCTG​(p.Asp164GlyfsTer2) variant causes a frameshift, stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,458,514 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SLC36A1 NM_078483.4 frameshift, stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.96
• Publications: 0 publications found

Genes affected

SLC36A1 (HGNC:18761): (solute carrier family 36 member 1) This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078483.4. 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
	SLC36A1	NM_078483.4	MANE Select	c.487_490dupGCTG	p.Asp164GlyfsTer2	frameshift stop_gained	Exon 6 of 11	NP_510968.2
	SLC36A1	NM_001349740.2		c.403_406dupGCTG	p.Asp136GlyfsTer2	frameshift stop_gained	Exon 7 of 12	NP_001336669.1
	SLC36A1	NM_001308150.2		c.487_490dupGCTG	p.Asp164GlyfsTer2	frameshift stop_gained	Exon 6 of 11	NP_001295079.1	Q7Z2H8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC36A1	ENST00000243389.8	TSL:1 MANE Select	c.487_490dupGCTG	p.Asp164GlyfsTer2	frameshift stop_gained	Exon 6 of 11	ENSP00000243389.3	Q7Z2H8-1
	SLC36A1	ENST00000521925.5	TSL:1	c.487_490dupGCTG	p.Asp164GlyfsTer2	frameshift stop_gained	Exon 6 of 10	ENSP00000430305.1	E7EW39
	SLC36A1	ENST00000429484.6	TSL:1	c.487_490dupGCTG	p.Asp164GlyfsTer2	frameshift stop_gained	Exon 6 of 9	ENSP00000395640.2	Q7Z2H8-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249706 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000617 AC: 9 AN: 1458514 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 725796

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110090

Other (OTH) AF: 0.00 AC: 0 AN: 60278

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Autism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0
Mutation Taster		=3/197	disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs755546492; hg19: chr5-150846823;