14-103102410-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001077594.2(EXOC3L4):c.687C>G(p.Pro229=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,532,906 control chromosomes in the GnomAD database, including 353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (188 hom., cov: 34)
  • Exomes 𝑓: 0.0031 (165 hom.)
• Consequence: EXOC3L4 NM_001077594.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.91

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-103102410-C-G is Benign according to our data. Variant chr14-103102410-C-G is described in ClinVar as [Benign]. Clinvar id is 1279821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC3L4	NM_001077594.2	c.687C>G	p.Pro229=	synonymous_variant	3/12	ENST00000688303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC3L4	ENST00000688303.1	c.687C>G	p.Pro229=	synonymous_variant	3/12		NM_001077594.2	P1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4166 AN: 152172 Hom.: 187 Cov.: 34

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00435 AC: 551 AN: 126658 Hom.: 8 AF XY: 0.00392 AC XY: 279 AN XY: 71236

Gnomad AFR exome AF: 0.0980

Gnomad AMR exome AF: 0.00445

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000114

Gnomad SAS exome AF: 0.00110

Gnomad FIN exome AF: 0.00112

Gnomad NFE exome AF: 0.000607

Gnomad OTH exome AF: 0.00451

GnomAD4 exome AF: 0.00311 AC: 4300 AN: 1380620 Hom.: 165 Cov.: 36 AF XY: 0.00273 AC XY: 1864 AN XY: 682934

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.00526

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000586

Gnomad4 SAS exome AF: 0.00156

Gnomad4 FIN exome AF: 0.000775

Gnomad4 NFE exome AF: 0.000506

Gnomad4 OTH exome AF: 0.00682

GnomAD4 genome AF: 0.0274 AC: 4168 AN: 152286 Hom.: 188 Cov.: 34 AF XY: 0.0263 AC XY: 1958 AN XY: 74466

Gnomad4 AFR AF: 0.0951

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.00165 Hom.: 1

Bravo AF: 0.0312

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 2020

This variant is associated with the following publications: (PMID: 30255815) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.087
Dann	Benign	0.58

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: rs10142287; hg19: chr14-103568747;