dbSNP rs16831541: SLC6A9:c.319+71C>T (chr1-44009894-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001024845.3(SLC6A9):c.319+71C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,556,440 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0069 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00064 ( 14 hom. )

Consequence

SLC6A9
NM_001024845.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.502

Publications

4 publications found

Variant links:

Genes affected

SLC6A9 (HGNC:11056): (solute carrier family 6 member 9) The amino acid glycine acts as an inhibitory neurotransmitter in the central nervous system. The protein encoded by this gene is one of two transporters that stop glycine signaling by removing it from the synaptic cleft. [provided by RefSeq, Jun 2016]

SLC6A9 Gene-Disease associations (from GenCC):

atypical glycine encephalopathy
Inheritance: Unknown, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen
infantile glycine encephalopathy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC6A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00692 (1054/152358) while in subpopulation AFR AF = 0.0245 (1017/41572). AF 95% confidence interval is 0.0232. There are 14 homozygotes in GnomAd4. There are 520 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC6A9	NM_001024845.3	MANE Select	c.319+71C>T	intron	N/A	NP_001020016.1	P48067-2
SLC6A9	NM_201649.4		c.538+71C>T	intron	N/A	NP_964012.2	P48067-1
SLC6A9	NM_006934.4		c.376+71C>T	intron	N/A	NP_008865.2	P48067-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC6A9	ENST00000372310.8	TSL:5 MANE Select	c.319+71C>T	intron	N/A	ENSP00000361384.4	P48067-2
SLC6A9	ENST00000360584.6	TSL:1	c.538+71C>T	intron	N/A	ENSP00000353791.2	P48067-1
SLC6A9	ENST00000357730.6	TSL:1	c.376+71C>T	intron	N/A	ENSP00000350362.2	P48067-3

Frequencies

GnomAD3 genomes

AF:

0.00682

AC:

1039

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.000642

AC:

901

AN:

1404082

Hom.:

AF XY:

0.000554

AC XY:

386

AN XY:

696336

show subpopulations

African (AFR)

AF:

0.0245

AC:

783

AN:

31964

American (AMR)

AF:

0.000804

AC:

AN:

41022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23434

East Asian (EAS)

AF:

0.00

AC:

AN:

39186

South Asian (SAS)

AF:

0.0000504

AC:

AN:

79290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51622

Middle Eastern (MID)

AF:

0.000439

AC:

AN:

4552

European-Non Finnish (NFE)

AF:

0.0000140

AC:

AN:

1075114

Other (OTH)

AF:

0.00111

AC:

AN:

57898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

107

143

179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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:

0.00692

AC:

1054

AN:

152358

Hom.:

Cov.:

AF XY:

0.00698

AC XY:

520

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0245

AC:

1017

AN:

41572

American (AMR)

AF:

0.00170

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68044

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00450

Hom.:

Bravo

AF:

0.00783

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.5

(source)

DANN

Benign

0.53

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over