chr15-89903962-G-T

Position:

• chr15-89903962-G-T

Variant summary

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

The NM_182616.4(ARPIN):​c.323C>A​(p.Thr108Asn) 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. 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: 3.41

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:38824): (ARPIN-AP3S2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring C15orf38 (chromosome 15 open reading frame 38) and AP3S2 (adaptor-related protein complex 3, sigma 2 subunit) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

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=0.22598985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPIN	NM_182616.4	c.323C>A	p.Thr108Asn	missense_variant	4/6	ENST00000357484.10	NP_872422.1
ARPIN-AP3S2	NM_001199058.2	c.323C>A	p.Thr108Asn	missense_variant	4/10		NP_001185987.1
ARPIN	NM_001282380.2	c.35C>A	p.Thr12Asn	missense_variant	4/6		NP_001269309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPIN	ENST00000357484.10	c.323C>A	p.Thr108Asn	missense_variant	4/6	1	NM_182616.4	ENSP00000350075.5
ARPIN-AP3S2	ENST00000398333.7	c.323C>A	p.Thr108Asn	missense_variant	4/10	2		ENSP00000381377.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Jul 05, 2024

The c.323C>A (p.T108N) alteration is located in exon 4 (coding exon 4) of the ARPIN gene. This alteration results from a C to A substitution at nucleotide position 323, causing the threonine (T) at amino acid position 108 to be replaced by an asparagine (N). 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	0.24
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;.;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.0	.;.;M;.
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.0020	D;.;D;D
Polyphen		0.34	.;.;B;.
Vest4		0.34
MutPred		0.44		Loss of phosphorylation at T108 (P = 0.0108);.;Loss of phosphorylation at T108 (P = 0.0108);.;
MVP		0.17
MPC		0.075
ClinPred		0.67	D
GERP RS		3.0
Varity_R		0.15
gMVP		0.52

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: chr15-90447194;