NM_178516.4:c.2147G>A

Variant names:

• chr16-67184488-C-T
• rs201102355
• NM_178516.4:c.2147G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_178516.4(EXOC3L1):​c.2147G>A​(p.Arg716His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00782 in 1,522,036 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R716C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0049 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0081 (55 hom.)
• Consequence: EXOC3L1 NM_178516.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.663
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00631842).
• BP6: Variant 16-67184488-C-T is Benign according to our data. Variant chr16-67184488-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2646610.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 55 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178516.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3L1	NM_178516.4	MANE Select	c.2147G>A	p.Arg716His	missense	Exon 14 of 14	NP_848611.2	Q86VI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3L1	ENST00000314586.11	TSL:2 MANE Select	c.2147G>A	p.Arg716His	missense	Exon 14 of 14	ENSP00000325674.6	Q86VI1
	EXOC3L1	ENST00000925360.1		c.2162G>A	p.Arg721His	missense	Exon 14 of 14	ENSP00000595419.1
	EXOC3L1	ENST00000925362.1		c.2162G>A	p.Arg721His	missense	Exon 14 of 14	ENSP00000595421.1

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 750 AN: 152094 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00922

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00538 AC: 649 AN: 120596 AF XY: 0.00579

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00191

Gnomad NFE exome AF: 0.00980

Gnomad OTH exome AF: 0.00322

GnomAD4 exome AF: 0.00814 AC: 11151 AN: 1369832 Hom.: 55 Cov.: 32 AF XY: 0.00812 AC XY: 5490 AN XY: 675846

African (AFR) AF: 0.00148 AC: 43 AN: 28986

American (AMR) AF: 0.00161 AC: 55 AN: 34090

Ashkenazi Jewish (ASJ) AF: 0.00209 AC: 51 AN: 24448

East Asian (EAS) AF: 0.0000290 AC: 1 AN: 34502

South Asian (SAS) AF: 0.00461 AC: 359 AN: 77856

European-Finnish (FIN) AF: 0.00218 AC: 73 AN: 33526

Middle Eastern (MID) AF: 0.00266 AC: 14 AN: 5256

European-Non Finnish (NFE) AF: 0.00955 AC: 10254 AN: 1073962

Other (OTH) AF: 0.00526 AC: 301 AN: 57206

GnomAD4 genome AF: 0.00493 AC: 751 AN: 152204 Hom.: 1 Cov.: 33 AF XY: 0.00445 AC XY: 331 AN XY: 74398

African (AFR) AF: 0.00157 AC: 65 AN: 41528

American (AMR) AF: 0.00157 AC: 24 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4830

European-Finnish (FIN) AF: 0.000755 AC: 8 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00922 AC: 627 AN: 68002

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00565 Hom.: 2

Bravo AF: 0.00490

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.00210 AC: 6

ESP6500EA AF: 0.00590 AC: 34

ExAC AF: 0.00277 AC: 130

Asia WGS AF: 0.00203 AC: 7 AN: 3468

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0062	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.66
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.22
Sift	Benign	0.13	T
Sift4G	Uncertain	0.044	D
Polyphen		1.0	D
Vest4		0.31
MVP		0.72
MPC		1.1
ClinPred		0.060	T
GERP RS		4.4
PromoterAI		0.093	Neutral
Varity_R		0.12
gMVP		0.66
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: rs201102355; hg19: chr16-67218391; COSMIC: COSV105012639; COSMIC: COSV105012639;