5-36629427-C-CTT

Position:

• chr5-36629427-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004172.5(SLC1A3):​c.182-9_182-8dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,451,346 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 29)
  • Exomes 𝑓: 0.0018 (1 hom.)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 5-36629427-C-CTT is Benign according to our data. Variant chr5-36629427-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 3341676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00181 (2373/1310842) while in subpopulation AFR AF= 0.0166 (498/30004). AF 95% confidence interval is 0.0154. There are 1 homozygotes in gnomad4_exome. There are 1128 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 505 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A3	NM_004172.5	c.182-9_182-8dup		intron_variant		ENST00000265113.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC1A3	ENST00000265113.9	c.182-9_182-8dup		intron_variant		1	NM_004172.5	P1

Frequencies

GnomAD3 genomes AF: 0.00357 AC: 501 AN: 140504 Hom.: 3 Cov.: 29

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000718

Gnomad ASJ AF: 0.000301

Gnomad EAS AF: 0.000206

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000621

Gnomad OTH AF: 0.00315

GnomAD4 exome AF: 0.00181 AC: 2373 AN: 1310842 Hom.: 1 Cov.: 0 AF XY: 0.00172 AC XY: 1128 AN XY: 656508

Gnomad4 AFR exome AF: 0.0166

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00138

Gnomad4 EAS exome AF: 0.00458

Gnomad4 SAS exome AF: 0.00187

Gnomad4 FIN exome AF: 0.000935

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00275

GnomAD4 genome AF: 0.00359 AC: 505 AN: 140504 Hom.: 3 Cov.: 29 AF XY: 0.00379 AC XY: 258 AN XY: 68060

Gnomad4 AFR AF: 0.0125

Gnomad4 AMR AF: 0.000718

Gnomad4 ASJ AF: 0.000301

Gnomad4 EAS AF: 0.000207

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000245

Gnomad4 NFE AF: 0.0000621

Gnomad4 OTH AF: 0.00314

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

SLC1A3: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs78316512; hg19: chr5-36629529;