Genetic Variant NM_004172.5:c.*1485C>T (chr5-36687754-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004172.5(SLC1A3):c.*1485C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,438 control chromosomes in the GnomAD database, including 3,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3018 hom., cov: 32)

Exomes 𝑓: 0.30 ( 18 hom. )

Consequence

SLC1A3
NM_004172.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0790

Publications

18 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 links:

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

SLC1A3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-36687754-C-T is Benign according to our data. Variant chr5-36687754-C-T is described in ClinVar as Benign. ClinVar VariationId is 353354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

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.*1485C>T	3_prime_UTR	Exon 10 of 10	NP_004163.3
SLC1A3	NM_001438458.1		c.*1485C>T	3_prime_UTR	Exon 11 of 11	NP_001425387.1
SLC1A3	NM_001438454.1		c.*1485C>T	3_prime_UTR	Exon 11 of 11	NP_001425383.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A3	ENST00000265113.9	TSL:1 MANE Select	c.*1485C>T	3_prime_UTR	Exon 10 of 10	ENSP00000265113.4	P43003-1
SLC1A3	ENST00000381918.4	TSL:1	c.*1485C>T	3_prime_UTR	Exon 10 of 10	ENSP00000371343.4	P43003-1
SLC1A3	ENST00000680232.1		c.*1485C>T	3_prime_UTR	Exon 11 of 11	ENSP00000506207.1	A0A7P0TAG7

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27746

AN:

151894

Hom.:

3017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0828

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.206

GnomAD4 exome

AF:

0.297

AC:

127

AN:

428

Hom.:

Cov.:

AF XY:

0.305

AC XY:

AN XY:

256

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.296

AC:

125

AN:

422

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.183

AC:

27759

AN:

152010

Hom.:

3018

Cov.:

AF XY:

0.188

AC XY:

14001

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0828

AC:

3432

AN:

41458

American (AMR)

AF:

0.295

AC:

4500

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

678

AN:

3470

East Asian (EAS)

AF:

0.268

AC:

1386

AN:

5178

South Asian (SAS)

AF:

0.190

AC:

911

AN:

4802

European-Finnish (FIN)

AF:

0.295

AC:

3108

AN:

10552

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13096

AN:

67974

Other (OTH)

AF:

0.205

AC:

433

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1100

2201

3301

4402

5502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.191

Hom.:

8453

Bravo

AF:

0.183

Asia WGS

AF:

0.207

AC:

717

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Episodic ataxia type 6 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.7

(source)

DANN

Benign

0.58

PhyloP100

-0.079

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over