5-1232257-GAG-CAA

Variant names:

• chr5-1232257-GAG-CAA
• NM_182632.3:c.199_201delGAGinsCAA
• SLC6A18 p.Glu67Gln

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_182632.3(SLC6A18):​c.199_201delGAGinsCAA​(p.Glu67Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E67K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC6A18 NM_182632.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.35
• Publications: 0 publications found

Genes affected

SLC6A18 (HGNC:26441): (solute carrier family 6 member 18) The SLC6 family of proteins, which includes SLC6A18, act as specific transporters for neurotransmitters, amino acids, and osmolytes like betaine, taurine, and creatine. SLC6 proteins are sodium cotransporters that derive the energy for solute transport from the electrochemical gradient for sodium ions (Hoglund et al., 2005 [PubMed 16125675]).[supplied by OMIM, Apr 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182632.3. 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
	SLC6A18	NM_182632.3	MANE Select	c.199_201delGAGinsCAA	p.Glu67Gln	missense	N/A	NP_872438.2	Q96N87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A18	ENST00000324642.4	TSL:1 MANE Select	c.199_201delGAGinsCAA	p.Glu67Gln	missense	N/A	ENSP00000323549.3	Q96N87
	SLC6A18	ENST00000513607.2	TSL:3	n.268_270delGAGinsCAA		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

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

hg19: chr5-1232372;