14-103102250-C-T

Variant names:

• chr14-103102250-C-T
• rs370099239
• NM_001077594.2:c.527C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001077594.2(EXOC3L4):​c.527C>T​(p.Ala176Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,587,606 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A176G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (2 hom.)
• Consequence: EXOC3L4 NM_001077594.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008429825).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC3L4	NM_001077594.2	c.527C>T	p.Ala176Val	missense_variant	Exon 3 of 12	ENST00000688303.1	NP_001071062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC3L4	ENST00000688303.1	c.527C>T	p.Ala176Val	missense_variant	Exon 3 of 12		NM_001077594.2	ENSP00000509130.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152258 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000344 AC: 69 AN: 200782 Hom.: 1 AF XY: 0.000463 AC XY: 51 AN XY: 110040

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000984

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00218

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000802

Gnomad OTH exome AF: 0.000190

GnomAD4 exome AF: 0.000159 AC: 228 AN: 1435230 Hom.: 2 Cov.: 31 AF XY: 0.000220 AC XY: 157 AN XY: 712210

Gnomad4 AFR exome AF: 0.0000912

Gnomad4 AMR exome AF: 0.0000720

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00190

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000436

Gnomad4 OTH exome AF: 0.000219

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152376 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74518

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000671 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.000341 AC: 41

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.0084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.087
Sift	Benign	0.21	T
Sift4G	Benign	0.59	T
Polyphen		0.90	P
Vest4		0.14
MVP		0.040
MPC		0.037
ClinPred		0.018	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.26

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: rs370099239; hg19: chr14-103568587;