14-103103964-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077594.2(EXOC3L4):c.1073G>A(p.Gly358Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: EXOC3L4 NM_001077594.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17

Genes affected

EXOC3L4 (HGNC:20120): (exocyst complex component 3 like 4) Predicted to enable SNARE binding activity. Predicted to be involved in exocyst localization and exocytosis. Predicted to be part of exocyst. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.04142028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC3L4	NM_001077594.2	c.1073G>A	p.Gly358Glu	missense_variant	4/12	ENST00000688303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC3L4	ENST00000688303.1	c.1073G>A	p.Gly358Glu	missense_variant	4/12		NM_001077594.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Sep 17, 2021

The c.1073G>A (p.G358E) alteration is located in exon 3 (coding exon 3) of the EXOC3L4 gene. This alteration results from a G to A substitution at nucleotide position 1073, causing the glycine (G) at amino acid position 358 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	Benign	0.088
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	15
Dann	Benign	0.97
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	0.10	T
Polyphen		0.010	B
Vest4		0.15
MutPred		0.49		Loss of loop (P = 0.0986);
MVP		0.014
MPC		1.2
ClinPred		0.088	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr14-103570301;