chr15-89908292-T-G

Position:

• chr15-89908292-T-G

Variant summary

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

The NM_182616.4(ARPIN):​c.289A>C​(p.Met97Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARPIN NM_182616.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81

Genes affected

ARPIN (HGNC:28782): (actin related protein 2/3 complex inhibitor) Involved in directional locomotion; negative regulation of cell migration; and negative regulation of cellular component organization. Predicted to be located in lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ARPIN-AP3S2 (HGNC:):

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/exons	MANE	UniProt
ARPIN	NM_182616.4	c.289A>C	p.Met97Leu	missense_variant	3/6	ENST00000357484.10
ARPIN-AP3S2	NM_001199058.2	c.289A>C	p.Met97Leu	missense_variant	3/10
ARPIN	NM_001282380.2	c.1A>C	p.Met1?	start_lost	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARPIN	ENST00000357484.10	c.289A>C	p.Met97Leu	missense_variant	3/6	1	NM_182616.4	P1
ARPIN	ENST00000460685.1	c.1A>C	p.Met1?	start_lost	3/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jan 23, 2023

The c.289A>C (p.M97L) alteration is located in exon 3 (coding exon 3) of the ARPIN gene. This alteration results from a A to C substitution at nucleotide position 289, causing the methionine (M) at amino acid position 97 to be replaced by a leucine (L). 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	0.12
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.92
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T;D;D;T;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.31	T;D;D;T;D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.63	T;T;D;T;T
Sift4G	Benign	0.48	T;.;.;T;T
Polyphen		0.0010	.;.;.;B;.
Vest4		0.45
MutPred		0.83		Loss of MoRF binding (P = 0.082);.;.;Loss of MoRF binding (P = 0.082);.;
MVP		0.13
MPC		0.050
ClinPred		0.21	T
GERP RS		1.2
Varity_R		0.066
gMVP		0.48

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: chr15-90451524;