rs1052123

Variant names:

• chr3-69105953-C-T
• rs1052123
• NM_006407.4:c.*1317C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006407.4(ARL6IP5):​c.*1317C>T variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARL6IP5 NM_006407.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

Genes affected

ARL6IP5 (HGNC:16937): (ADP ribosylation factor like GTPase 6 interacting protein 5) Expression of this gene is affected by vitamin A. The encoded protein of this gene may be associated with the cytoskeleton. A similar protein in rats may play a role in the regulation of cell differentiation. The rat protein binds and inhibits the cell membrane glutamate transporter EAAC1. The expression of the rat gene is upregulated by retinoic acid, which results in a specific reduction in EAAC1-mediated glutamate transport. [provided by RefSeq, Jul 2008]

LMOD3 (HGNC:6649): (leiomodin 3) The protein encoded by this gene is a member of the leiomodin family of proteins. This protein contains three actin-binding domains, a tropomyosin domain, a leucine-rich repeat domain, and a Wiskott-Aldrich syndrome protein homology 2 domain (WH2). Localization of this protein to the pointed ends of thin filaments has been observed, and there is evidence that this protein acts as a catalyst of actin nucleation, and is important to the organization of sarcomeric thin filaments in skeletal muscles. Mutations in this gene have been associated as one cause of Nemaline myopathy, as other genes have also been linked to this disorder. Nemaline myopathy is a disorder characterized by nonprogressive generalized muscle weakness and protein inclusions (nemaline bodies) in skeletal myofibers. Patients with mutations in this gene often present with a severe congenital form of the disorder. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL6IP5	NM_006407.4	c.*1317C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000273258.4	NP_006398.1
LMOD3	NM_198271.5	c.*3142G>A		downstream_gene_variant		ENST00000420581.7	NP_938012.2
LMOD3	NM_001304418.3	c.*3142G>A		downstream_gene_variant			NP_001291347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL6IP5	ENST00000273258.4	c.*1317C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_006407.4	ENSP00000273258.3
ARL6IP5	ENST00000478935.1	c.*1044C>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000420138.1
LMOD3	ENST00000420581.7	c.*3142G>A		downstream_gene_variant		1	NM_198271.5	ENSP00000414670.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.4
DANN	Benign	0.69

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: rs1052123; hg19: chr3-69155104;