Variant 17-3723958-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031965.2(HASPIN):c.23C>T(p.Pro8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,417,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000014 ( 0 hom. )

Consequence

HASPIN
NM_031965.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.122

Variant links:

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]

HASPIN links:

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]

ITGAE links:

ITGAE (HGNC:):

ITGAE links:

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ACMG classification

Classification made for transcript

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=0.06739816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HASPIN	NM_031965.2 linkuse as main transcript	c.23C>T	p.Pro8Leu	missense_variant	1/1	ENST00000325418.5	NP_114171.2	Q8TF76-1A0PJ70
ITGAE	NM_002208.5 linkuse as main transcript	c.3085-214G>A		intron_variant		ENST00000263087.9	NP_002199.3	P38570

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HASPIN	ENST00000325418.5 linkuse as main transcript	c.23C>T	p.Pro8Leu	missense_variant	1/1	6	NM_031965.2	ENSP00000325290.4	Q8TF76-1
ITGAE	ENST00000263087.9 linkuse as main transcript	c.3085-214G>A		intron_variant		1	NM_002208.5	ENSP00000263087.4	P38570
ITGAE	ENST00000570415.5 linkuse as main transcript	n.479-214G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000474

AC:

AN:

210818

Hom.:

AF XY:

0.00

AC XY:

AN XY:

117612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000342

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000141

AC:

AN:

1417096

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700514

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000256

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:

9.18e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000843

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2024

The c.23C>T (p.P8L) alteration is located in exon 1 (coding exon 1) of the GSG2 gene. This alteration results from a C to T substitution at nucleotide position 23, causing the proline (P) at amino acid position 8 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.8

DANN

Benign

0.85

DEOGEN2

Benign

0.054

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.36

M_CAP

Benign

0.029

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.59

REVEL

Benign

0.042

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.017

Polyphen

0.0010

Vest4

0.15

MutPred

0.16

Loss of glycosylation at P8 (P = 0.018);

MVP

0.17

MPC

0.39

ClinPred

0.090

GERP RS

0.051

Varity_R

0.039

gMVP

0.19

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over