GeneBe

NM_005629.4:c.262+6T>G

Variant names:

Variant summary

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

Score: -2 - Likely Benign
-2
-12 -7 -6 -1 0 5 6 9 10 12
PM2BP4_Strong

The NM_005629.4(SLC6A8):​c.262+6T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 21)
Exomes 𝑓: 0.0000031 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

SLC6A8
NM_005629.4 splice_region, intron

Scores

2
Splicing: ADA: 0.001840
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.821

Publications

0 publications found
Variant links:
Genes affected
SLC6A8 (HGNC:11055): (solute carrier family 6 member 8) The protein encoded by this gene is a plasma membrane protein whose function is to transport creatine into and out of cells. Defects in this gene can result in X-linked creatine deficiency syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]
PNCK (HGNC:13415): (pregnancy up-regulated nonubiquitous CaM kinase) PNCK is a member of the calcium/calmodulin-dependent protein kinase family of protein serine/threonine kinases (see CAMK1; MIM 604998) (Gardner et al., 2000 [PubMed 10673339]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=-0.85).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC6A8NM_005629.4 linkc.262+6T>G splice_region_variant, intron_variant Intron 1 of 12 ENST00000253122.10 NP_005620.1 P48029-1X5D9C4
SLC6A8NM_001142805.2 linkc.262+6T>G splice_region_variant, intron_variant Intron 1 of 12 NP_001136277.1 P48029Q59EV7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC6A8ENST00000253122.10 linkc.262+6T>G splice_region_variant, intron_variant Intron 1 of 12 1 NM_005629.4 ENSP00000253122.5 P48029-1
PNCKENST00000480693.1 linkn.37A>C non_coding_transcript_exon_variant Exon 1 of 4 5
PNCKENST00000458354.5 linkc.-30A>C 5_prime_UTR_variant Exon 1 of 4 3 ENSP00000401542.1 C9J2B9
SLC6A8ENST00000476466.1 linkn.114+6T>G splice_region_variant, intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000310
AC:
3
AN:
968571
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
296263
show subpopulations
⚠️ 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:
20783
American (AMR)
AF:
0.00
AC:
0
AN:
25691
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15514
East Asian (EAS)
AF:
0.00
AC:
0
AN:
21723
South Asian (SAS)
AF:
0.00
AC:
0
AN:
41771
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
35527
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2579
European-Non Finnish (NFE)
AF:
0.00000392
AC:
3
AN:
766058
Other (OTH)
AF:
0.00
AC:
0
AN:
38925
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.242
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
8.7
DANN
Benign
0.82
PhyloP100
-0.82
PromoterAI
-0.11
Neutral

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0018
dbscSNV1_RF
Benign
0.044
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs878853039; hg19: chrX-152954297; API