14-103100256-C-A

Position:

• chr14-103100256-C-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.37C>A​(p.Leu13Met) 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. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EXOC3L4 NM_001077594.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.668

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=0.03901899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC3L4	NM_001077594.2	c.37C>A	p.Leu13Met	missense_variant	2/12	ENST00000688303.1	NP_001071062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC3L4	ENST00000688303.1	c.37C>A	p.Leu13Met	missense_variant	2/12		NM_001077594.2	ENSP00000509130.1
EXOC3L4	ENST00000380069.7	c.37C>A	p.Leu13Met	missense_variant	1/11	1		ENSP00000369409.3
EXOC3L4	ENST00000687959.1	c.37C>A	p.Leu13Met	missense_variant	3/13			ENSP00000508483.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426962 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 706370

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Mar 19, 2024

The c.37C>A (p.L13M) alteration is located in exon 1 (coding exon 1) of the EXOC3L4 gene. This alteration results from a C to A substitution at nucleotide position 37, causing the leucine (L) at amino acid position 13 to be replaced by a methionine (M). 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	0.096
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.9
DANN	Benign	0.75
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.028
Sift	Benign	0.25	T
Sift4G	Benign	0.22	T
Polyphen		0.028	B
Vest4		0.12
MutPred		0.13		Loss of loop (P = 0.1242);
MVP		0.014
MPC		0.041
ClinPred		0.27	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.15

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: chr14-103566593;