chr5-36671025-C-A

Variant names:

• chr5-36671025-C-A
• rs760934282
• NM_004172.5:c.320-4C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_004172.5(SLC1A3):​c.320-4C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC1A3 NM_004172.5 splice_region, intron
• Scores: Splicing: ADA: 0.0004926
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.48
• Publications: 0 publications found

Genes affected

SLC1A3 (HGNC:10941): (solute carrier family 1 member 3) This gene encodes a member of a member of a high affinity glutamate transporter family. This gene functions in the termination of excitatory neurotransmission in central nervous system. Mutations are associated with episodic ataxia, Type 6. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2014]

SLC1A3-AS1 (HGNC:56374): (SLC1A3 antisense RNA 1)

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=-0.26).
• BP6: Variant 5-36671025-C-A is Benign according to our data. Variant chr5-36671025-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1612689.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004172.5. 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
	SLC1A3	NM_004172.5	MANE Select	c.320-4C>A		splice_region intron	N/A	NP_004163.3
	SLC1A3	NM_001438458.1		c.320-4C>A		splice_region intron	N/A	NP_001425387.1
	SLC1A3	NM_001438454.1		c.320-4C>A		splice_region intron	N/A	NP_001425383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.320-4C>A		splice_region intron	N/A	ENSP00000265113.4	P43003-1
	SLC1A3	ENST00000381918.4	TSL:1	c.320-4C>A		splice_region intron	N/A	ENSP00000371343.4	P43003-1
	SLC1A3	ENST00000680232.1		c.320-4C>A		splice_region intron	N/A	ENSP00000506207.1	A0A7P0TAG7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461380 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727020

⚠️ 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: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111618

Other (OTH) AF: 0.00 AC: 0 AN: 60374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0249301), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.90
PhyloP100		2.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00049
dbscSNV1_RF	Benign	0.022
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: rs760934282; hg19: chr5-36671127;