20-38724868-C-A

Variant names:

• chr20-38724868-C-A
• NM_080552.3:c.144C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_080552.3(SLC32A1):​c.144C>A​(p.Asp48Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC32A1 NM_080552.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.246
• Publications: 0 publications found

Genes affected

SLC32A1 (HGNC:11018): (solute carrier family 32 member 1) The protein encoded by this gene is an integral membrane protein involved in gamma-aminobutyric acid (GABA) and glycine uptake into synaptic vesicles. The encoded protein is a member of amino acid/polyamine transporter family II. [provided by RefSeq, Jul 2008]

SLC32A1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 114

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P
• generalized epilepsy with febrile seizures plus, type 12

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ENSG00000301653 (HGNC:):

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 6 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 2.3023 (below the threshold of 3.09). Trascript score misZ: 3.4509 (above the threshold of 3.09). GenCC associations: The gene is linked to developmental and epileptic encephalopathy 114.
• BP4: Computational evidence support a benign effect (MetaRNN=0.35148662).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080552.3. 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
	SLC32A1	NM_080552.3	MANE Select	c.144C>A	p.Asp48Glu	missense	Exon 1 of 2	NP_542119.1	Q9H598

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC32A1	ENST00000217420.2	TSL:1 MANE Select	c.144C>A	p.Asp48Glu	missense	Exon 1 of 2	ENSP00000217420.1	Q9H598
	ENSG00000301653	ENST00000780566.1		n.84+2632G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.25
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.11
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.033	D
Polyphen		0.44	B
Vest4		0.65
MutPred		0.40		Gain of loop (P = 0.1069)
MVP		0.44
ClinPred		0.84	D
GERP RS		2.9
PromoterAI		-0.053	Neutral
Varity_R		0.20
gMVP		0.48
Mutation Taster		=50/50

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

hg19: chr20-37353511;