chr16-67185374-T-C

Position:

• chr16-67185374-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178516.4(EXOC3L1):​c.1613A>G​(p.Gln538Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: EXOC3L1 NM_178516.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0100

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16924658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC3L1	NM_178516.4	c.1613A>G	p.Gln538Arg	missense_variant	10/14	ENST00000314586.11	NP_848611.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC3L1	ENST00000314586.11	c.1613A>G	p.Gln538Arg	missense_variant	10/14	2	NM_178516.4	ENSP00000325674.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460562 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726648

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.1613A>G (p.Q538R) alteration is located in exon 10 (coding exon 9) of the EXOC3L1 gene. This alteration results from a A to G substitution at nucleotide position 1613, causing the glutamine (Q) at amino acid position 538 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.0032	T;.;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.34	N;N;N
REVEL	Benign	0.069
Sift	Uncertain	0.021	D;T;T
Sift4G	Uncertain	0.033	D;.;T
Polyphen		0.81	P;P;.
Vest4		0.31
MutPred		0.68		Gain of MoRF binding (P = 0.0348);.;.;
MVP		0.37
MPC		1.4
ClinPred		0.20	T
GERP RS		2.8
Varity_R		0.060
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67219277;