17-3724251-C-G

Variant names:

• chr17-3724251-C-G
• rs369981279
• NM_031965.2:c.316C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031965.2(HASPIN):​c.316C>G​(p.Arg106Gly) 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. 14/22 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. R106C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HASPIN NM_031965.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10749698).

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.316C>G	p.Arg106Gly	missense	Exon 1 of 1	NP_114171.2	A0PJ70
	ITGAE	NM_002208.5	MANE Select	c.3085-507G>C		intron	N/A	NP_002199.3
	ITGAE	NM_001425071.1		c.3007-507G>C		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.316C>G	p.Arg106Gly	missense	Exon 1 of 1	ENSP00000325290.4	Q8TF76-1
	ITGAE	ENST00000263087.9	TSL:1 MANE Select	c.3085-507G>C		intron	N/A	ENSP00000263087.4	P38570
	ITGAE	ENST00000949198.1		c.3181-507G>C		intron	N/A	ENSP00000619257.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 212360 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.24
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.052
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.029	D
Polyphen		0.89	P
Vest4		0.13
MutPred		0.25		Loss of stability (P = 0.0216)
MVP		0.25
MPC		0.50
ClinPred		0.18	T
GERP RS		0.64
PromoterAI		0.072	Neutral
Varity_R		0.16
gMVP		0.20

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: rs369981279; hg19: chr17-3627545;