rs778228093

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080466.2(BTBD17):​c.1257G>C​(p.Gln419His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BTBD17
NM_001080466.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77
Variant links:
Genes affected
BTBD17 (HGNC:33758): (BTB domain containing 17) Predicted to be involved in negative regulation of viral genome replication and response to virus. Predicted to be located in plasma membrane. Predicted to colocalize with cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13693428).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTBD17NM_001080466.2 linkc.1257G>C p.Gln419His missense_variant Exon 3 of 3 ENST00000375366.4 NP_001073935.1 A6NE02
BTBD17XM_011524791.3 linkc.1260G>C p.Gln420His missense_variant Exon 5 of 5 XP_011523093.1
BTBD17XM_017024622.2 linkc.1260G>C p.Gln420His missense_variant Exon 5 of 5 XP_016880111.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTBD17ENST00000375366.4 linkc.1257G>C p.Gln419His missense_variant Exon 3 of 3 1 NM_001080466.2 ENSP00000364515.3 A6NE02

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152056
Hom.:
0
Cov.:
33
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1413476
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
701692
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
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
152056
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74276
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000852
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 28, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1257G>C (p.Q419H) alteration is located in exon 3 (coding exon 3) of the BTBD17 gene. This alteration results from a G to C substitution at nucleotide position 1257, causing the glutamine (Q) at amino acid position 419 to be replaced by a histidine (H). 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
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.096
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
16
DANN
Benign
0.94
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.52
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.2
L
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.16
Sift
Benign
0.16
T
Sift4G
Benign
0.099
T
Polyphen
0.0020
B
Vest4
0.14
MutPred
0.38
Gain of sheet (P = 0.0101);
MVP
0.65
ClinPred
0.097
T
GERP RS
-0.86
Varity_R
0.053
gMVP
0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs778228093; hg19: chr17-72352976; API