NM_001080523.3:c.862C>A

Variant names:

• chr19-4891171-G-T
• rs781375501
• NM_001080523.3:c.862C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001080523.3(ARRDC5):​c.862C>A​(p.Pro288Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P288A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARRDC5 NM_001080523.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04
• Publications: 0 publications found

Genes affected

ARRDC5 (HGNC:31407): (arrestin domain containing 5) Predicted to enable ubiquitin ligase-substrate adaptor activity and ubiquitin protein ligase binding activity. Predicted to be involved in protein transport. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080523.3. 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
	ARRDC5	NM_001080523.3	MANE Select	c.862C>A	p.Pro288Thr	missense	Exon 3 of 3	NP_001073992.2	A0A494BZV3
	ARRDC5	NM_001367189.2		c.928C>A	p.Pro310Thr	missense	Exon 4 of 4	NP_001354118.1	A0ABB0MV98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARRDC5	ENST00000650722.2	MANE Select	c.862C>A	p.Pro288Thr	missense	Exon 3 of 3	ENSP00000498235.1	A0A494BZV3
	ARRDC5	ENST00000718248.1		c.928C>A	p.Pro310Thr	missense	Exon 4 of 4	ENSP00000520693.1	A0ABB0MV98
	ARRDC5	ENST00000718249.1		n.*468C>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000520694.1	A0ABB0MV92

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461704 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727134

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.24
Sift	Benign	0.058	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.52		Gain of sheet (P = 0.1208)
MVP		0.29
MPC		0.58
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.29
gMVP		0.80
Mutation Taster		=93/7	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: rs781375501; hg19: chr19-4891183;