17-44148992-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001171251.3(HROB):c.1189C>T(p.Arg397Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
HROB
NM_001171251.3 missense
NM_001171251.3 missense
Scores
6
7
5
Clinical Significance
Conservation
PhyloP100: 3.10
Genes affected
HROB (HGNC:28460): (homologous recombination factor with OB-fold) Predicted to enable single-stranded DNA binding activity. Involved in DNA synthesis involved in DNA repair and interstrand cross-link repair. Located in site of DNA damage. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HROB | NM_001171251.3 | c.1189C>T | p.Arg397Cys | missense_variant | 3/10 | ENST00000585683.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HROB | ENST00000585683.6 | c.1189C>T | p.Arg397Cys | missense_variant | 3/10 | 2 | NM_001171251.3 | A2 | |
HROB | ENST00000319977.8 | c.1189C>T | p.Arg397Cys | missense_variant | 3/10 | 1 | P4 | ||
HROB | ENST00000245382.6 | c.1189C>T | p.Arg397Cys | missense_variant | 3/7 | 1 | |||
HROB | ENST00000588434.1 | n.1222C>T | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250488Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135460
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461692Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727132
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2021 | The c.1189C>T (p.R397C) alteration is located in exon 3 (coding exon 3) of the C17orf53 gene. This alteration results from a C to T substitution at nucleotide position 1189, causing the arginine (R) at amino acid position 397 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D
PROVEAN
Pathogenic
D;.;D
REVEL
Benign
Sift
Pathogenic
D;.;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at