chr15-40458762-C-T

Variant summary

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

The NM_014952.5(BAHD1):​c.298C>T​(p.Pro100Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

BAHD1
NM_014952.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38
Variant links:
Genes affected
BAHD1 (HGNC:29153): (bromo adjacent homology domain containing 1) Enables chromatin binding activity. Involved in heterochromatin assembly and negative regulation of transcription, DNA-templated. Located in nucleoplasm. Part of chromatin silencing complex. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.1336084).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BAHD1NM_014952.5 linkc.298C>T p.Pro100Ser missense_variant Exon 2 of 7 ENST00000416165.6 NP_055767.3 Q8TBE0-1A0A024R9K2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BAHD1ENST00000416165.6 linkc.298C>T p.Pro100Ser missense_variant Exon 2 of 7 1 NM_014952.5 ENSP00000396976.1 Q8TBE0-1
BAHD1ENST00000561234.5 linkc.298C>T p.Pro100Ser missense_variant Exon 2 of 7 1 ENSP00000454150.1 Q8TBE0-2
BAHD1ENST00000560846.1 linkc.298C>T p.Pro100Ser missense_variant Exon 1 of 6 1 ENSP00000454101.1 Q8TBE0-3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
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
GnomAD3 exomes
AF:
0.00000404
AC:
1
AN:
247748
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134698
show subpopulations
Gnomad AFR exome
AF:
0.0000645
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000482
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
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
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 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.298C>T (p.P100S) alteration is located in exon 2 (coding exon 1) of the BAHD1 gene. This alteration results from a C to T substitution at nucleotide position 298, causing the proline (P) at amino acid position 100 to be replaced by a serine (S). 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
0.084
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
23
DANN
Uncertain
0.97
DEOGEN2
Benign
0.083
.;T;.
Eigen
Benign
-0.068
Eigen_PC
Benign
0.076
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.85
T;T;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.20
N;N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.50
N;N;N
REVEL
Benign
0.16
Sift
Benign
0.13
T;T;T
Sift4G
Benign
0.79
T;T;T
Polyphen
0.90
P;P;P
Vest4
0.27
MutPred
0.14
Gain of phosphorylation at P100 (P = 0.0013);Gain of phosphorylation at P100 (P = 0.0013);Gain of phosphorylation at P100 (P = 0.0013);
MVP
0.51
MPC
0.85
ClinPred
0.26
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.050
gMVP
0.14

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: rs778734004; hg19: chr15-40750961; COSMIC: COSV101346715; COSMIC: COSV101346715; API