dbSNP rs1238846540: HROB:p.His64Asn (chr17-44147993-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001171251.3(HROB):c.190C>A(p.His64Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. H64Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HROB
NM_001171251.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.155

Variant links:

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]

HROB links:

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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=0.08320284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HROB	NM_001171251.3 link	c.190C>A	p.His64Asn	missense_variant	Exon 3 of 10	ENST00000585683.6	NP_001164722.1	Q8N3J3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HROB	ENST00000585683.6 link	c.190C>A	p.His64Asn	missense_variant	Exon 3 of 10	2	NM_001171251.3	ENSP00000466618.1	Q8N3J3-4
HROB	ENST00000319977.8 link	c.190C>A	p.His64Asn	missense_variant	Exon 3 of 10	1		ENSP00000313500.4	Q8N3J3-1
HROB	ENST00000245382.6 link	c.190C>A	p.His64Asn	missense_variant	Exon 3 of 7	1		ENSP00000245382.5	Q8N3J3-3
HROB	ENST00000588434.1 link	n.223C>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251232

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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

AF:

0.00000137

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.92

DANN

Benign

0.54

DEOGEN2

Benign

0.0067

T;.;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.083

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L

PROVEAN

Benign

-1.1

N;.;N

REVEL

Benign

0.010

Sift

Benign

0.33

T;.;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.26

B;.;B

Vest4

0.13

MutPred

0.13

Loss of catalytic residue at L63 (P = 0.1462);Loss of catalytic residue at L63 (P = 0.1462);Loss of catalytic residue at L63 (P = 0.1462);

MVP

0.30

MPC

0.14

ClinPred

0.059

GERP RS

0.67

Varity_R

0.030

gMVP

0.054

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over