rs1462664984

Variant summary

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

The NM_033067.3(DMRTB1):​c.341G>A​(p.Arg114His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000398 in 1,257,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R114L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

DMRTB1
NM_033067.3 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0440
Variant links:
Genes affected
DMRTB1 (HGNC:13913): (DMRT like family B with proline rich C-terminal 1) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in germ cell development; regulation of transcription by RNA polymerase II; and sex differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [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=0.12681058).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DMRTB1NM_033067.3 linkc.341G>A p.Arg114His missense_variant Exon 1 of 4 ENST00000371445.3 NP_149056.1 Q96MA1I6L9A0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DMRTB1ENST00000371445.3 linkc.341G>A p.Arg114His missense_variant Exon 1 of 4 1 NM_033067.3 ENSP00000360500.3 Q96MA1
DMRTB1ENST00000463126.1 linkn.-182G>A upstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000398
AC:
5
AN:
1257556
Hom.:
0
Cov.:
31
AF XY:
0.00000324
AC XY:
2
AN XY:
617420
show subpopulations
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:
0.0000152
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000393
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
12
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0037
T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.62
T
M_CAP
Benign
0.067
D
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.050
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.019
D
Polyphen
0.97
D
Vest4
0.12
MutPred
0.28
Loss of methylation at R114 (P = 0.0074);
MVP
0.068
MPC
0.62
ClinPred
0.24
T
GERP RS
-0.023
Varity_R
0.059
gMVP
0.098

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: chr1-53925467; API