17-3724098-G-C

Variant names:

• chr17-3724098-G-C
• rs1282457480
• NM_031965.2:c.163G>C

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.163G>C​(p.Gly55Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HASPIN NM_031965.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.567
• Publications: 1 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=0.09917095).

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.163G>C	p.Gly55Arg	missense	Exon 1 of 1	NP_114171.2	A0PJ70
	ITGAE	NM_002208.5	MANE Select	c.3085-354C>G		intron	N/A	NP_002199.3
	ITGAE	NM_001425071.1		c.3007-354C>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.163G>C	p.Gly55Arg	missense	Exon 1 of 1	ENSP00000325290.4	Q8TF76-1
	ITGAE	ENST00000263087.9	TSL:1 MANE Select	c.3085-354C>G		intron	N/A	ENSP00000263087.4	P38570
	ITGAE	ENST00000949198.1		c.3181-354C>G		intron	N/A	ENSP00000619257.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000912 AC: 2 AN: 219400 AF XY: 0.0000164

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000593

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 AF: 0.00000208 AC: 3 AN: 1442832 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 718038

African (AFR) AF: 0.00 AC: 0 AN: 32624

American (AMR) AF: 0.0000677 AC: 3 AN: 44306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39424

South Asian (SAS) AF: 0.00 AC: 0 AN: 85910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109524

Other (OTH) AF: 0.00 AC: 0 AN: 59848

GnomAD4 genome Cov.: 33

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	0.13
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.3
DANN	Benign	0.97
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.57
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.044
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.017	D
Polyphen		0.74	P
Vest4		0.10
MutPred		0.26		Gain of solvent accessibility (P = 0.019)
MVP		0.27
MPC		0.89
ClinPred		0.60	D
GERP RS		-1.9
PromoterAI		-0.011	Neutral
Varity_R		0.072
gMVP		0.078

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: rs1282457480; hg19: chr17-3627392;