rs10131298

chr14-103102277-T-Achr14-103102277-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077594.2(EXOC3L4):c.554T>A(p.Leu185His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,580,606 control chromosomes in the GnomAD database, including 47,530 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (4639 hom., cov: 34)
  • Exomes 𝑓: 0.24 (42891 hom.)
• Consequence: EXOC3L4 NM_001077594.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024491847).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXOC3L4	NM_001077594.2	c.554T>A	p.Leu185His	missense_variant	3/12	ENST00000688303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXOC3L4	ENST00000688303.1	c.554T>A	p.Leu185His	missense_variant	3/12		NM_001077594.2	P1
EXOC3L4	ENST00000380069.7	c.554T>A	p.Leu185His	missense_variant	2/11	1		P1
EXOC3L4	ENST00000687959.1	c.554T>A	p.Leu185His	missense_variant	4/13			P1
EXOC3L4	ENST00000559116.1	c.286+1664T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36928 AN: 152066 Hom.: 4628 Cov.: 34

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.262

GnomAD3 exomes AF: 0.240 AC: 47122 AN: 196358 Hom.: 5756 AF XY: 0.244 AC XY: 26386 AN XY: 108136

Gnomad AFR exome AF: 0.270

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.257

Gnomad SAS exome AF: 0.271

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.247

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.244 AC: 348539 AN: 1428422 Hom.: 42891 Cov.: 36 AF XY: 0.245 AC XY: 173603 AN XY: 708518

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.243

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.243 AC: 36975 AN: 152184 Hom.: 4639 Cov.: 34 AF XY: 0.240 AC XY: 17886 AN XY: 74414

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.264

Alfa AF: 0.240 Hom.: 1349

Bravo AF: 0.244

TwinsUK AF: 0.249 AC: 922

ALSPAC AF: 0.246 AC: 949

ESP6500AA AF: 0.264 AC: 1155

ESP6500EA AF: 0.242 AC: 2075

ExAC AF: 0.219 AC: 26025

Asia WGS AF: 0.276 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	15
Dann	Benign	0.94
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.8	N
MutationTaster	Benign	0.66	P
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.046
Sift	Benign	0.053	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.14
MPC		0.041
ClinPred		0.0077	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.061
gMVP		0.74

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: rs10131298; hg19: chr14-103568614; COSMIC: COSV66295382; COSMIC: COSV66295382;