9-137612988-C-G

Position:

• chr9-137612988-C-G

Variant summary

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

The NM_152285.4(ARRDC1):​c.211C>G​(p.Leu71Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: ARRDC1 NM_152285.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.372

Genes affected

ARRDC1 (HGNC:28633): (arrestin domain containing 1) Enables several functions, including arrestin family protein binding activity; ubiquitin ligase-substrate adaptor activity; and ubiquitin protein ligase binding activity. Involved in several processes, including cellular protein metabolic process; extracellular vesicle biogenesis; and negative regulation of Notch signaling pathway. Located in cytoplasmic vesicle; extracellular vesicle; and plasma membrane. [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=0.075699955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARRDC1	NM_152285.4	c.211C>G	p.Leu71Val	missense_variant	2/8	ENST00000371421.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARRDC1	ENST00000371421.9	c.211C>G	p.Leu71Val	missense_variant	2/8	1	NM_152285.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

May 31, 2023

The c.211C>G (p.L71V) alteration is located in exon 2 (coding exon 2) of the ARRDC1 gene. This alteration results from a C to G substitution at nucleotide position 211, causing the leucine (L) at amino acid position 71 to be replaced by a valine (V). 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	0.096
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.0038	T;.;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.091	N
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.;.
MutationTaster	Benign	0.83	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.63	N;N;N
REVEL	Benign	0.050
Sift	Benign	0.49	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.30	B;.;B
Vest4		0.39
MutPred		0.45		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.16
MPC		0.27
ClinPred		0.55	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
gMVP		0.40

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: chr9-140507440;