17-3724380-G-C

Variant names:

• chr17-3724380-G-C
• rs2051154924
• NM_031965.2:c.445G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031965.2(HASPIN):​c.445G>C​(p.Asp149His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HASPIN NM_031965.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

Genes affected

HASPIN (HGNC:19682): (histone H3 associated protein kinase) Enables ATP binding activity and histone kinase activity (H3-T3 specific). Involved in histone H3-T3 phosphorylation involved in chromosome passenger complex localization to kinetochore; intracellular signal transduction; and mitotic sister chromatid cohesion. Located in centrosome; nucleoplasm; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ITGAE (HGNC:6147): (integrin subunit alpha E) Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This gene encodes an I-domain-containing alpha integrin that undergoes post-translational cleavage in the extracellular domain, yielding disulfide-linked heavy and light chains. In combination with the beta 7 integrin, this protein forms the E-cadherin binding integrin known as the human mucosal lymphocyte-1 antigen. This protein is preferentially expressed in human intestinal intraepithelial lymphocytes (IEL), and in addition to a role in adhesion, it may serve as an accessory molecule for IEL activation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29211438).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031965.2. 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
	HASPIN	NM_031965.2	MANE Select	c.445G>C	p.Asp149His	missense	Exon 1 of 1	NP_114171.2	A0PJ70
	ITGAE	NM_002208.5	MANE Select	c.3085-636C>G		intron	N/A	NP_002199.3
	ITGAE	NM_001425071.1		c.3007-636C>G		intron	N/A	NP_001412000.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HASPIN	ENST00000325418.5	TSL:6 MANE Select	c.445G>C	p.Asp149His	missense	Exon 1 of 1	ENSP00000325290.4	Q8TF76-1
	ITGAE	ENST00000263087.9	TSL:1 MANE Select	c.3085-636C>G		intron	N/A	ENSP00000263087.4	P38570
	ITGAE	ENST00000949198.1		c.3181-636C>G		intron	N/A	ENSP00000619257.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.14
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.089
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.29
MutPred		0.35		Gain of catalytic residue at D149 (P = 0.1322)
MVP		0.45
MPC		1.2
ClinPred		0.95	D
GERP RS		3.5
PromoterAI		-0.12	Neutral
Varity_R		0.36
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2051154924; hg19: chr17-3627674;