rs1396089145

Variant names:

• chr16-67184924-A-C
• rs1396089145
• NM_178516.4:c.1883T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-67184924-A-C
• chr16-67184924-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_178516.4(EXOC3L1):​c.1883T>G​(p.Leu628Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. L628P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EXOC3L1 NM_178516.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31

Genes affected

EXOC3L1 (HGNC:27540): (exocyst complex component 3 like 1) Predicted to enable SNARE binding activity. Predicted to be involved in exocyst localization; exocytosis; and peptide hormone secretion. Predicted to be located in secretory granule. Predicted to be part of exocyst. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.963

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXOC3L1	NM_178516.4	c.1883T>G	p.Leu628Arg	missense_variant	Exon 12 of 14	ENST00000314586.11	NP_848611.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXOC3L1	ENST00000314586.11	c.1883T>G	p.Leu628Arg	missense_variant	Exon 12 of 14	2	NM_178516.4	ENSP00000325674.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.96	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0	D;.;D
Polyphen		1.0	D;D;.
Vest4		0.86
MutPred		0.91		Gain of disorder (P = 0.0174);.;.;
MVP		0.64
MPC		2.4
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.87
gMVP		0.89

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: rs1396089145; hg19: chr16-67218827;