17-44148179-A-G

Position:

• chr17-44148179-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001171251.3(HROB):​c.376A>G​(p.Thr126Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 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. T126P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HROB NM_001171251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043552995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HROB	NM_001171251.3	c.376A>G	p.Thr126Ala	missense_variant	3/10	ENST00000585683.6	NP_001164722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HROB	ENST00000585683.6	c.376A>G	p.Thr126Ala	missense_variant	3/10	2	NM_001171251.3	ENSP00000466618	A2
HROB	ENST00000319977.8	c.376A>G	p.Thr126Ala	missense_variant	3/10	1		ENSP00000313500	P4
HROB	ENST00000245382.6	c.376A>G	p.Thr126Ala	missense_variant	3/7	1		ENSP00000245382
HROB	ENST00000588434.1	n.409A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.0025	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.31	T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.044	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.060	N;.;N
REVEL	Benign	0.040
Sift	Benign	0.092	T;.;D
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.093
MutPred		0.097		Loss of phosphorylation at T126 (P = 0.0297);Loss of phosphorylation at T126 (P = 0.0297);Loss of phosphorylation at T126 (P = 0.0297);
MVP		0.22
MPC		0.12
ClinPred		0.041	T
GERP RS		1.5
Varity_R		0.032
gMVP		0.067

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

Other links and lift over

dbSNP: rs227584; hg19: chr17-42225547;