NM_012106.4:c.190C>T

Variant names:

• chr16-57248626-C-T
• rs2075398122
• NM_012106.4:c.190C>T

Variant summary

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

The NM_012106.4(ARL2BP):​c.190C>T​(p.Pro64Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARL2BP NM_012106.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

Genes affected

ARL2BP (HGNC:17146): (ADP ribosylation factor like GTPase 2 binding protein) ADP-ribosylation factor (ARF)-like proteins (ARLs) comprise a functionally distinct group of the ARF family of RAS-related GTPases. The protein encoded by this gene binds to ARL2.GTP with high affinity but does not interact with ARL2.GDP, activated ARF, or RHO proteins. The lack of detectable membrane association of this protein or ARL2 upon activation of ARL2 is suggestive of actions distinct from those of the ARFs. This protein is considered to be the first ARL2-specific effector identified, due to its interaction with ARL2.GTP but lack of ARL2 GTPase-activating protein activity. [provided by RefSeq, Jul 2008]

PLLP (HGNC:18553): (plasmolipin) Predicted to be a structural constituent of myelin sheath. Predicted to be involved in myelination. Predicted to be located in compact myelin and membrane raft. Predicted to be integral component of membrane. Biomarker of schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903697 (HGNC:):

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=0.1001766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL2BP	NM_012106.4	c.190C>T	p.Pro64Ser	missense_variant	Exon 3 of 6	ENST00000219204.8	NP_036238.1
ARL2BP	XM_047433883.1	c.94C>T	p.Pro32Ser	missense_variant	Exon 3 of 6		XP_047289839.1
LOC124903697	XR_007065082.1	n.1435G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL2BP	ENST00000219204.8	c.190C>T	p.Pro64Ser	missense_variant	Exon 3 of 6	1	NM_012106.4	ENSP00000219204.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.064
Sift	Benign	0.24	T
Sift4G	Benign	0.47	T
Polyphen		0.033	B
Vest4		0.21
MutPred		0.28		Loss of loop (P = 0.0804);
MVP		0.26
MPC		0.51
ClinPred		0.25	T
GERP RS		4.8
Varity_R		0.15
gMVP		0.56

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

LitVar

Other links and lift over

dbSNP: rs2075398122; hg19: chr16-57282538;