Variant 9-27294397-A-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.208T>A(p.Phe70Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000464 in 1,591,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

EQTN
NM_020641.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

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=0.13108826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EQTN	NM_020641.3 linkuse as main transcript	c.208T>A	p.Phe70Ile	missense_variant	3/8	ENST00000380032.8
EQTN	NM_001161585.2 linkuse as main transcript	c.208T>A	p.Phe70Ile	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EQTN	ENST00000380032.8 linkuse as main transcript	c.208T>A	p.Phe70Ile	missense_variant	3/8	1	NM_020641.3	P1	Q9NQ60-1
EQTN	ENST00000537675.5 linkuse as main transcript	c.208T>A	p.Phe70Ile	missense_variant	3/7	1			Q9NQ60-3
EQTN	ENST00000380031.2 linkuse as main transcript	c.208T>A	p.Phe70Ile	missense_variant	3/4	1			Q9NQ60-2
EQTN	ENST00000484994.1 linkuse as main transcript	n.227T>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000193

AC:

AN:

249216

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

134694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

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:

0.000406

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000484

AC:

696

AN:

1439050

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

330

AN XY:

714700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000903

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.0000391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000597

Gnomad4 OTH exome

AF:

0.000523

GnomAD4 genome

AF:

0.000276

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.000321

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000181

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

May 27, 2022

The c.208T>A (p.F70I) alteration is located in exon 3 (coding exon 3) of the EQTN gene. This alteration results from a T to A substitution at nucleotide position 208, causing the phenylalanine (F) at amino acid position 70 to be replaced by an isoleucine (I). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.065

T;.;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.010

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

0.65

P;.;P

Vest4

0.66

MVP

0.19

MPC

0.0054

ClinPred

0.13

GERP RS

3.5

Varity_R

0.20

gMVP

0.35

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