Variant chr9-27284955-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020641.3(EQTN):c.653G>A(p.Ser218Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,180 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

EQTN
NM_020641.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.460

Variant links:

Genes affected

EQTN (HGNC:1359): (equatorin) Predicted to be involved in acrosomal vesicle exocytosis; endocytosis; and fusion of sperm to egg plasma membrane involved in single fertilization. Predicted to be located in acrosomal membrane; early endosome; and nucleus. Predicted to be active in inner acrosomal membrane; outer acrosomal membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EQTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0752126).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EQTN	NM_020641.3 linkuse as main transcript	c.653G>A	p.Ser218Asn	missense_variant	8/8	ENST00000380032.8
EQTN	NM_001161585.2 linkuse as main transcript	c.566G>A	p.Ser189Asn	missense_variant	7/7
EQTN	XM_011517920.2 linkuse as main transcript	c.245G>A	p.Ser82Asn	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EQTN	ENST00000380032.8 linkuse as main transcript	c.653G>A	p.Ser218Asn	missense_variant	8/8	1	NM_020641.3	P1	Q9NQ60-1
EQTN	ENST00000537675.5 linkuse as main transcript	c.566G>A	p.Ser189Asn	missense_variant	7/7	1			Q9NQ60-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249314

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134680

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460180

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726228

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Jul 25, 2023

The c.653G>A (p.S218N) alteration is located in exon 8 (coding exon 8) of the EQTN gene. This alteration results from a G to A substitution at nucleotide position 653, causing the serine (S) at amino acid position 218 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.6

DANN

Benign

0.97

DEOGEN2

Benign

0.039

T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.075

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.020

Sift

Uncertain

0.020

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

0.11

B;.

Vest4

0.066

MutPred

0.17

Gain of relative solvent accessibility (P = 0.0479);.;

MVP

0.072

MPC

0.017

ClinPred

0.21

GERP RS

-2.3

Varity_R

0.11

gMVP

0.023

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