chr17-43400082-A-G

Position:

• chr17-43400082-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP3 BP6

The ENST00000320033.5(ARL4D):​c.350A>G​(p.His117Arg) 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. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARL4D ENST00000320033.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.43

Genes affected

ARL4D (HGNC:656): (ADP ribosylation factor like GTPase 4D) ADP-ribosylation factor 4D is a member of the ADP-ribosylation factor family of GTP-binding proteins. ARL4D is closely similar to ARL4A and ARL4C and each has a nuclear localization signal and an unusually high guanine nucleotide exchange rate. This protein may play a role in membrane-associated intracellular trafficking. [provided by RefSeq, Jul 2021]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813
• BP6: Variant 17-43400082-A-G is Benign according to our data. Variant chr17-43400082-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2681403.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL4D	NM_001661.4	c.350A>G	p.His117Arg	missense_variant	2/2	ENST00000320033.5	NP_001652.2
ARL4D	XM_011524782.3	c.350A>G	p.His117Arg	missense_variant	2/2		XP_011523084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL4D	ENST00000320033.5	c.350A>G	p.His117Arg	missense_variant	2/2	1	NM_001661.4	ENSP00000322628	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.33
Sift	Benign	0.039	D
Sift4G	Benign	0.17	T
Polyphen		0.97	D
Vest4		0.76
MutPred		0.48		Gain of MoRF binding (P = 0.0105);
MVP		0.75
MPC		2.4
ClinPred		0.92	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.69
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-41477450;