Variant 6-138210011-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_020340.5(ARFGEF3):c.321C>T(p.Leu107Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,613,796 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 27 hom. )

Consequence

ARFGEF3
NM_020340.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

ARFGEF3 (HGNC:21213): (ARFGEF family member 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in transport vesicle membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARFGEF3 links:

ARFGEF3 (HGNC:):

ARFGEF3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 6-138210011-C-T is Benign according to our data. Variant chr6-138210011-C-T is described in ClinVar as [Benign]. Clinvar id is 715845.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00129 (197/152282) while in subpopulation SAS AF= 0.0235 (113/4810). AF 95% confidence interval is 0.02. There are 1 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFGEF3	NM_020340.5 linkuse as main transcript	c.321C>T	p.Leu107Leu	synonymous_variant	4/34	ENST00000251691.5	NP_065073.3	Q5TH69
ARFGEF3	XR_001743524.2 linkuse as main transcript	n.469C>T		non_coding_transcript_exon_variant	4/35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF3	ENST00000251691.5 linkuse as main transcript	c.321C>T	p.Leu107Leu	synonymous_variant	4/34	1	NM_020340.5	ENSP00000251691.4		Q5TH69

Frequencies

GnomAD3 genomes

AF:

0.00129

AC:

196

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0233

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00331

AC:

831

AN:

250798

Hom.:

AF XY:

0.00426

AC XY:

577

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.000708

Gnomad SAS exome

AF:

0.0242

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00155

AC:

2263

AN:

1461514

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

1570

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0225

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00129

AC:

197

AN:

152282

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

129

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0235

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000442

Hom.:

Bravo

AF:

0.000672

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000534

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

8.1

DANN

Benign

0.77

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over