9-27286290-C-T

Position:

• chr9-27286290-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020641.3(EQTN):​c.554G>A​(p.Gly185Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: EQTN NM_020641.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EQTN	NM_020641.3	c.554G>A	p.Gly185Glu	missense_variant	7/8	ENST00000380032.8
EQTN	NM_001161585.2	c.467G>A	p.Gly156Glu	missense_variant	6/7
EQTN	XM_011517920.2	c.146G>A	p.Gly49Glu	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EQTN	ENST00000380032.8	c.554G>A	p.Gly185Glu	missense_variant	7/8	1	NM_020641.3	P1
EQTN	ENST00000537675.5	c.467G>A	p.Gly156Glu	missense_variant	6/7	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459904 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725924

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.554G>A (p.G185E) alteration is located in exon 7 (coding exon 7) of the EQTN gene. This alteration results from a G to A substitution at nucleotide position 554, causing the glycine (G) at amino acid position 185 to be replaced by a glutamic acid (E). 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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.97	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-7.3	D;D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.73
MutPred		0.42		Gain of ubiquitination at K181 (P = 0.0725);.;
MVP		0.48
MPC		0.023
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.84
gMVP		0.075

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

Other links and lift over

dbSNP: rs1169731906; hg19: chr9-27286288;