19-14968175-G-T

Variant names:

• chr19-14968175-G-T
• rs2097837
• NM_005071.3:c.548+128C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005071.3(SLC1A6):​c.548+128C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 592,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SLC1A6 NM_005071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

Genes affected

SLC1A6 (HGNC:10944): (solute carrier family 1 member 6) Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005071.3. 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
	SLC1A6	NM_005071.3	MANE Select	c.548+128C>A		intron	N/A	NP_005062.1
	SLC1A6	NM_001384669.1		c.548+128C>A		intron	N/A	NP_001371598.1
	SLC1A6	NM_001272087.2		c.548+128C>A		intron	N/A	NP_001259016.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A6	ENST00000594383.2	TSL:2 MANE Select	c.548+128C>A		intron	N/A	ENSP00000472133.2
	SLC1A6	ENST00000221742.7	TSL:1	c.548+128C>A		intron	N/A	ENSP00000221742.3
	SLC1A6	ENST00000600144.5	TSL:1	c.548+128C>A		intron	N/A	ENSP00000471038.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000169 AC: 1 AN: 592210 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 304812

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

African (AFR) AF: 0.00 AC: 0 AN: 15296

American (AMR) AF: 0.00 AC: 0 AN: 22982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15192

East Asian (EAS) AF: 0.00 AC: 0 AN: 31580

South Asian (SAS) AF: 0.00 AC: 0 AN: 49696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2376

European-Non Finnish (NFE) AF: 0.00000256 AC: 1 AN: 390898

Other (OTH) AF: 0.00 AC: 0 AN: 30830

⚠️ 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 Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.2
DANN	Benign	0.46
PhyloP100		1.1

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: rs2097837; hg19: chr19-15078987;