rs375269398

Variant names:

• chr17-3724105-C-A
• NM_031965.2:c.170C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-3724105-C-A
• chr17-3724105-C-T

Variant summary

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

The NM_031965.2(HASPIN):​c.170C>A​(p.Pro57His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,442,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HASPIN NM_031965.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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

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=0.04695174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HASPIN	NM_031965.2	c.170C>A	p.Pro57His	missense_variant	Exon 1 of 1	ENST00000325418.5	NP_114171.2
ITGAE	NM_002208.5	c.3085-361G>T		intron_variant	Intron 26 of 30	ENST00000263087.9	NP_002199.3
ITGAE	NM_001425071.1	c.3007-361G>T		intron_variant	Intron 25 of 29		NP_001412000.1
ITGAE	NM_001425072.1	c.3085-3703G>T		intron_variant	Intron 26 of 28		NP_001412001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HASPIN	ENST00000325418.5	c.170C>A	p.Pro57His	missense_variant	Exon 1 of 1	6	NM_031965.2	ENSP00000325290.4
ITGAE	ENST00000263087.9	c.3085-361G>T		intron_variant	Intron 26 of 30	1	NM_002208.5	ENSP00000263087.4
ITGAE	ENST00000570415.5	n.479-361G>T		intron_variant	Intron 2 of 6	3
ITGAE	ENST00000571185.1	n.*213G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442964 Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2 AN XY: 718156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.91
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.040
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Polyphen		0.012	B
Vest4		0.084
MutPred		0.12		Gain of catalytic residue at P57 (P = 0.0696);
MVP		0.30
MPC		0.45
ClinPred		0.054	T
GERP RS		-2.2
Varity_R		0.054
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3627399;