14-103100448-C-G

Variant names:

• chr14-103100448-C-G
• rs2297067
• NM_001077594.2:c.229C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077594.2(EXOC3L4):​c.229C>G​(p.Arg77Gly) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EXOC3L4 NM_001077594.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098391354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC3L4	NM_001077594.2	c.229C>G	p.Arg77Gly	missense_variant	Exon 2 of 12	ENST00000688303.1	NP_001071062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC3L4	ENST00000688303.1	c.229C>G	p.Arg77Gly	missense_variant	Exon 2 of 12		NM_001077594.2	ENSP00000509130.1
EXOC3L4	ENST00000380069.7	c.229C>G	p.Arg77Gly	missense_variant	Exon 1 of 11	1		ENSP00000369409.3
EXOC3L4	ENST00000687959.1	c.229C>G	p.Arg77Gly	missense_variant	Exon 3 of 13			ENSP00000508483.1
EXOC3L4	ENST00000559116.1	c.121C>G	p.Arg41Gly	missense_variant	Exon 1 of 3	5		ENSP00000454163.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	10
DANN	Benign	0.89
DEOGEN2	Benign	0.0086	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PhyloP100		-0.47
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.5	N;D
REVEL	Benign	0.10
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.96	D;.
Vest4		0.14
MutPred		0.28		Loss of MoRF binding (P = 0.0196);.;
MVP		0.048
MPC		0.047
ClinPred		0.45	T
GERP RS		-6.1
PromoterAI		-0.064	Neutral
Varity_R		0.10
gMVP		0.17
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs2297067; hg19: chr14-103566785;