3-57276619-ACG-GCA

Variant names:

• chr3-57276619-ACG-GCA
• NM_001142733.3:c.1693_1695delCGTinsTGC
• ASB14 p.Arg565Cys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001142733.3(ASB14):​c.1693_1695delCGTinsTGC​(p.Arg565Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R565S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ASB14 NM_001142733.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 0 publications found

Genes affected

ASB14 (HGNC:19766): (ankyrin repeat and SOCS box containing 14) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2008]

APPL1 (HGNC:24035): (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus. [provided by RefSeq, Jul 2008]

APPL1 Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young type 14

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• monogenic diabetes

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

LOC105377102 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142733.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB14	NM_001142733.3	MANE Select	c.1693_1695delCGTinsTGC	p.Arg565Cys	missense	N/A	NP_001136205.2	A6NK59-3
	ASB14	NM_130387.5		c.838_840delCGTinsTGC	p.Arg280Cys	missense	N/A	NP_569058.1	A6NK59-2
	LOC105377102	NR_135535.1		n.342+160_342+162delACGinsGCA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB14	ENST00000487349.6	TSL:1 MANE Select	c.1693_1695delCGTinsTGC	p.Arg565Cys	missense	N/A	ENSP00000419199.1	A6NK59-3
	ASB14	ENST00000515033.1	TSL:1	n.838_840delCGTinsTGC		non_coding_transcript_exon	Exon 3 of 3
	APPL1	ENST00000855520.1		c.*14-1174_*14-1172delACGinsGCA		intron	N/A	ENSP00000525579.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-57310647;