17-44148179-A-T

Variant names:

• chr17-44148179-A-T
• rs227584
• NM_001171251.3:c.376A>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.376A>T​(p.Thr126Ser) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HROB NM_001171251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 94 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=0.031386912).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HROB	NM_001171251.3	MANE Select	c.376A>T	p.Thr126Ser	missense	Exon 3 of 10	NP_001164722.1
	HROB	NM_024032.5		c.376A>T	p.Thr126Ser	missense	Exon 3 of 10	NP_076937.2
	HROB	NM_001321311.2		c.376A>T	p.Thr126Ser	missense	Exon 3 of 10	NP_001308240.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HROB	ENST00000585683.6	TSL:2 MANE Select	c.376A>T	p.Thr126Ser	missense	Exon 3 of 10	ENSP00000466618.1
	HROB	ENST00000319977.8	TSL:1	c.376A>T	p.Thr126Ser	missense	Exon 3 of 10	ENSP00000313500.4
	HROB	ENST00000245382.6	TSL:1	c.376A>T	p.Thr126Ser	missense	Exon 3 of 7	ENSP00000245382.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.1
DANN	Benign	0.34
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.81	N
PhyloP100		-0.13
PROVEAN	Benign	0.28	N
REVEL	Benign	0.045
Sift	Benign	0.51	T
Sift4G	Benign	0.84	T
Polyphen		0.0	B
Vest4		0.053
MutPred		0.098		Loss of glycosylation at T126 (P = 0.0764)
MVP		0.19
MPC		0.11
ClinPred		0.020	T
GERP RS		1.5
Varity_R		0.025
gMVP		0.066

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: rs227584; hg19: chr17-42225547;