chr17-44147993-C-T

Variant names:

• chr17-44147993-C-T
• rs1238846540
• NM_001171251.3:c.190C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001171251.3(HROB):​c.190C>T​(p.His64Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HROB NM_001171251.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.155
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044716835).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171251.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HROB	NM_001171251.3	MANE Select	c.190C>T	p.His64Tyr	missense	Exon 3 of 10	NP_001164722.1	Q8N3J3-4
	HROB	NM_024032.5		c.190C>T	p.His64Tyr	missense	Exon 3 of 10	NP_076937.2
	HROB	NM_001321311.2		c.190C>T	p.His64Tyr	missense	Exon 3 of 10	NP_001308240.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HROB	ENST00000585683.6	TSL:2 MANE Select	c.190C>T	p.His64Tyr	missense	Exon 3 of 10	ENSP00000466618.1	Q8N3J3-4
	HROB	ENST00000319977.8	TSL:1	c.190C>T	p.His64Tyr	missense	Exon 3 of 10	ENSP00000313500.4	Q8N3J3-1
	HROB	ENST00000245382.6	TSL:1	c.190C>T	p.His64Tyr	missense	Exon 3 of 7	ENSP00000245382.5	Q8N3J3-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152168 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461738 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727182

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152168 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.27
DANN	Benign	0.18
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.15
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.053
Sift	Benign	0.77	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.051
MutPred		0.14		Gain of catalytic residue at P68 (P = 0.0867)
MVP		0.17
MPC		0.14
ClinPred		0.015	T
GERP RS		0.67
Varity_R		0.022
gMVP		0.073

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

Other links and lift over

dbSNP: rs1238846540; hg19: chr17-42225361;