2-27212208-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021095.4(SLC5A6):​c.-396T>C variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SLC5A6
NM_021095.4 5_prime_UTR

Scores

2
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.521
Variant links:
Genes affected
ATRAID (HGNC:24090): (all-trans retinoic acid induced differentiation factor) This gene is thought to be involved in apoptosis, and may also be involved in hematopoietic development and differentiation. The use of alternative splice sites and promotors result in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2009]
SLC5A6 (HGNC:11041): (solute carrier family 5 member 6) Enables biotin transmembrane transporter activity and pantothenate transmembrane transporter activity. Involved in anion transmembrane transport and transport across blood-brain barrier. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14234176).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATRAIDNM_001170795.4 linkuse as main transcriptc.-161A>G 5_prime_UTR_variant 1/7 ENST00000380171.9 NP_001164266.1
SLC5A6NM_021095.4 linkuse as main transcriptc.-396T>C 5_prime_UTR_variant 1/17 ENST00000310574.8 NP_066918.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC5A6ENST00000310574.8 linkuse as main transcriptc.-396T>C 5_prime_UTR_variant 1/171 NM_021095.4 ENSP00000310208 P1
ATRAIDENST00000380171.9 linkuse as main transcriptc.-161A>G 5_prime_UTR_variant 1/71 NM_001170795.4 ENSP00000369518 P1Q6UW56-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1403758
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
693182
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 20, 2024The c.5A>G (p.K2R) alteration is located in exon 1 (coding exon 1) of the ATRAID gene. This alteration results from a A to G substitution at nucleotide position 5, causing the lysine (K) at amino acid position 2 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
11
DANN
Uncertain
0.99
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.43
.;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
1.0
N;D
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.080
N;.
REVEL
Benign
0.11
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.10
B;B
Vest4
0.036
MutPred
0.21
Loss of ubiquitination at K2 (P = 4e-04);Loss of ubiquitination at K2 (P = 4e-04);
MVP
0.34
MPC
0.17
ClinPred
0.98
D
GERP RS
3.8
gMVP
0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27435076; API