9-27286266-A-G

Position:

• chr9-27286266-A-G

Variant summary

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

The NM_020641.3(EQTN):​c.578T>C​(p.Leu193Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EQTN NM_020641.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

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	Protein	UniProt
EQTN	NM_020641.3	c.578T>C	p.Leu193Pro	missense_variant	7/8	ENST00000380032.8	NP_065692.2
EQTN	NM_001161585.2	c.491T>C	p.Leu164Pro	missense_variant	6/7		NP_001155057.1
EQTN	XM_011517920.2	c.170T>C	p.Leu57Pro	missense_variant	4/5		XP_011516222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EQTN	ENST00000380032.8	c.578T>C	p.Leu193Pro	missense_variant	7/8	1	NM_020641.3	ENSP00000369371.3
EQTN	ENST00000537675.5	c.491T>C	p.Leu164Pro	missense_variant	6/7	1		ENSP00000441630.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Jul 16, 2021

The c.578T>C (p.L193P) alteration is located in exon 7 (coding exon 7) of the EQTN gene. This alteration results from a T to C substitution at nucleotide position 578, causing the leucine (L) at amino acid position 193 to be replaced by a proline (P). 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	0.78
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.78
MutPred		0.53		Loss of stability (P = 0.0081);.;
MVP		0.44
MPC		0.021
ClinPred		0.91	D
GERP RS		4.7
Varity_R		0.78
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-27286264;