chr19-4891171-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARRDC5	NM_001080523.3	c.862C>A	p.Pro288Thr	missense_variant	Exon 3 of 3	ENST00000650722.2	NP_001073992.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARRDC5	ENST00000650722.2	c.862C>A	p.Pro288Thr	missense_variant	Exon 3 of 3		NM_001080523.3	ENSP00000498235.1
ARRDC5	ENST00000381781.2	c.904C>A	p.Pro302Thr	missense_variant	Exon 3 of 3	3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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: chr19-4891183;