5-36629442-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004172.5(SLC1A3):c.182-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000684 in 1,607,552 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: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

SLC1A3
NM_004172.5 splice_region, intron

Scores

Splicing: ADA: 0.000008181

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.69

Publications

0 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

episodic ataxia type 6
Inheritance: AD, Unknown Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Laboratory for Molecular Medicine

SLC1A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 5-36629442-T-C is Benign according to our data. Variant chr5-36629442-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 586620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 7 AD,Unknown gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC1A3	NM_004172.5	MANE Select	c.182-8T>C	splice_region intron	N/A	NP_004163.3
SLC1A3	NM_001438458.1		c.182-8T>C	splice_region intron	N/A	NP_001425387.1
SLC1A3	NM_001438454.1		c.182-8T>C	splice_region intron	N/A	NP_001425383.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.182-8T>C	splice_region intron	N/A	ENSP00000265113.4
SLC1A3	ENST00000381918.4	TSL:1	c.182-8T>C	splice_region intron	N/A	ENSP00000371343.4
SLC1A3	ENST00000680232.1		c.182-8T>C	splice_region intron	N/A	ENSP00000506207.1

Frequencies

GnomAD3 genomes

AF:

0.0000463

AC:

AN:

151068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.000836

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000154

AC:

AN:

247126

AF XY:

0.000180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000589

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000625

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000707

AC:

103

AN:

1456374

Hom.:

Cov.:

AF XY:

0.0000952

AC XY:

AN XY:

724512

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33126

American (AMR)

AF:

0.0000679

AC:

AN:

44190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26034

East Asian (EAS)

AF:

0.00

AC:

AN:

39636

South Asian (SAS)

AF:

0.00100

AC:

AN:

85584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000902

AC:

AN:

1108912

Other (OTH)

AF:

0.0000665

AC:

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000463

AC:

AN:

151178

Hom.:

Cov.:

AF XY:

0.0000542

AC XY:

AN XY:

73832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41298

American (AMR)

AF:

0.00

AC:

AN:

15194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000390

AC:

AN:

5134

South Asian (SAS)

AF:

0.000836

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67750

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000770

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 19, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 01, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.032

(source)

DANN

Benign

0.29

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000082

dbscSNV1_RF

Benign

0.0

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over