1-44808897-C-T

Variant summary

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

The NM_001136537.3(BTBD19):​c.77C>T​(p.Pro26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,549,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

BTBD19
NM_001136537.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33
Variant links:
Genes affected
BTBD19 (HGNC:27145): (BTB domain containing 19)

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=0.11859846).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BTBD19NM_001136537.3 linkc.77C>T p.Pro26Leu missense_variant Exon 1 of 8 ENST00000450269.6 NP_001130009.1 C9JJ37-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BTBD19ENST00000450269.6 linkc.77C>T p.Pro26Leu missense_variant Exon 1 of 8 5 NM_001136537.3 ENSP00000395461.1 C9JJ37-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000258
AC:
4
AN:
154894
Hom.:
0
AF XY:
0.0000365
AC XY:
3
AN XY:
82142
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000409
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000934
Gnomad SAS exome
AF:
0.0000442
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000167
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000122
AC:
17
AN:
1397418
Hom.:
0
Cov.:
30
AF XY:
0.00000580
AC XY:
4
AN XY:
689338
show subpopulations
Gnomad4 AFR exome
AF:
0.0000317
Gnomad4 AMR exome
AF:
0.0000281
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000121
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152286
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000697
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.77C>T (p.P26L) alteration is located in exon 1 (coding exon 1) of the BTBD19 gene. This alteration results from a C to T substitution at nucleotide position 77, causing the proline (P) at amino acid position 26 to be replaced by a leucine (L). 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
0.22
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T;.
Eigen
Benign
0.084
Eigen_PC
Benign
0.015
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.82
T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-2.0
N;N
REVEL
Uncertain
0.37
Sift
Benign
0.046
D;D
Sift4G
Uncertain
0.037
D;D
Polyphen
0.98
D;.
Vest4
0.43
MutPred
0.58
Loss of catalytic residue at P26 (P = 0.0179);Loss of catalytic residue at P26 (P = 0.0179);
MVP
0.28
ClinPred
0.35
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.22
gMVP
0.32

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: rs544769415; hg19: chr1-45274569; API