rs1555494322

Variant names:

• chr16-8781387-T-A
• rs1555494322
• NM_020686.6:c.1460T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-8781387-T-A
• chr16-8781387-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_001386615.1(ABAT):​c.1556T>A​(p.Leu519Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. 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. L519P) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABAT NM_001386615.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02
• Publications: 0 publications found

Genes affected

ABAT (HGNC:23): (4-aminobutyrate aminotransferase) 4-aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. The protein sequence is over 95% similar to the pig protein. GABA is estimated to be present in nearly one-third of human synapses. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44. The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

TMEM186 (HGNC:24530): (transmembrane protein 186) This gene encodes a potential transmembrane protein. [provided by RefSeq, Dec 2012]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr16-8781387-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 438387.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.19670758).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386615.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	NM_020686.6	MANE Select	c.1460T>A	p.Leu487Gln	missense	Exon 16 of 16	NP_065737.2
	ABAT	NM_001386615.1		c.1556T>A	p.Leu519Gln	missense	Exon 17 of 17	NP_001373544.1
	ABAT	NM_001386616.1		c.1519T>A	p.Cys507Ser	missense	Exon 16 of 16	NP_001373545.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABAT	ENST00000268251.13	TSL:1 MANE Select	c.1460T>A	p.Leu487Gln	missense	Exon 16 of 16	ENSP00000268251.8
	ABAT	ENST00000569156.5	TSL:1	c.1519T>A	p.Cys507Ser	missense	Exon 16 of 16	ENSP00000454963.1
	ABAT	ENST00000566590.5	TSL:1	n.*1200T>A		non_coding_transcript_exon	Exon 15 of 15	ENSP00000455198.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T
PhyloP100		6.0
PROVEAN	Benign	0.48	N
Sift	Pathogenic	0.0	D
Vest4		0.17
MVP		0.88
ClinPred		0.90	D
GERP RS		5.4
Varity_R		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1555494322; hg19: chr16-8875244;