chr11-61300817-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001923.5(DDB1):​c.3331A>C​(p.Asn1111His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

DDB1
NM_001923.5 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.69
Variant links:
Genes affected
DDB1 (HGNC:2717): (damage specific DNA binding protein 1) The protein encoded by this gene is the large subunit (p127) of the heterodimeric DNA damage-binding (DDB) complex while another protein (p48) forms the small subunit. This protein complex functions in nucleotide-excision repair and binds to DNA following UV damage. Defective activity of this complex causes the repair defect in patients with xeroderma pigmentosum complementation group E (XPE) - an autosomal recessive disorder characterized by photosensitivity and early onset of carcinomas. However, it remains for mutation analysis to demonstrate whether the defect in XPE patients is in this gene or the gene encoding the small subunit. In addition, Best vitelliform mascular dystrophy is mapped to the same region as this gene on 11q, but no sequence alternations of this gene are demonstrated in Best disease patients. The protein encoded by this gene also functions as an adaptor molecule for the cullin 4 (CUL4) ubiquitin E3 ligase complex by facilitating the binding of substrates to this complex and the ubiquitination of proteins. [provided by RefSeq, May 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DDB1. . Gene score misZ 4.8864 (greater than the threshold 3.09). Trascript score misZ 6.4521 (greater than threshold 3.09). GenCC has associacion of gene with White-Kernohan syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.23329052).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DDB1NM_001923.5 linkuse as main transcriptc.3331A>C p.Asn1111His missense_variant 26/27 ENST00000301764.12 NP_001914.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDB1ENST00000301764.12 linkuse as main transcriptc.3331A>C p.Asn1111His missense_variant 26/271 NM_001923.5 ENSP00000301764 P1Q16531-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
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
-0.026
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.11
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.26
Sift
Benign
0.092
T
Sift4G
Benign
0.15
T
Polyphen
0.0
B
Vest4
0.34
MutPred
0.32
Loss of stability (P = 0.0925);
MVP
0.58
MPC
1.5
ClinPred
0.63
D
GERP RS
5.8
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.8
Varity_R
0.55
gMVP
0.59

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: chr11-61068289; API