chr3-57269520-C-CT

Variant names:

• chr3-57269520-C-CT
• rs146184583
• NM_001142733.3:c.*120dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001142733.3(ASB14):​c.*120dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 1,609,890 control chromosomes in the GnomAD database, including 433 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (21 hom., cov: 32)
  • Exomes 𝑓: 0.021 (412 hom.)
• Consequence: ASB14 NM_001142733.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.06
• 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: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-57269520-C-CT is Benign according to our data. Variant chr3-57269520-C-CT is described in ClinVar as Benign. ClinVar VariationId is 2428543.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0129 (1964/152230) while in subpopulation NFE AF = 0.0232 (1576/68010). AF 95% confidence interval is 0.0222. There are 21 homozygotes in GnomAd4. There are 879 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

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.*120dupA		3_prime_UTR	Exon 11 of 11	NP_001136205.2	A6NK59-3
	APPL1	NM_012096.3	MANE Select	c.1984-15dupT		intron	N/A	NP_036228.1	Q9UKG1
	ASB14	NM_130387.5		c.*120dupA		3_prime_UTR	Exon 4 of 4	NP_569058.1	A6NK59-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB14	ENST00000487349.6	TSL:1 MANE Select	c.*120dupA		3_prime_UTR	Exon 11 of 11	ENSP00000419199.1	A6NK59-3
	APPL1	ENST00000288266.8	TSL:1 MANE Select	c.1984-15dupT		intron	N/A	ENSP00000288266.3	Q9UKG1
	APPL1	ENST00000855520.1		c.1984-15dupT		intron	N/A	ENSP00000525579.1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1965 AN: 152112 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00413

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00662

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00736

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.0127 AC: 3150 AN: 247538 AF XY: 0.0128

Gnomad AFR exome AF: 0.00339

Gnomad AMR exome AF: 0.00505

Gnomad ASJ exome AF: 0.00498

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00802

Gnomad NFE exome AF: 0.0232

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.0214 AC: 31221 AN: 1457660 Hom.: 412 Cov.: 30 AF XY: 0.0207 AC XY: 15012 AN XY: 724754

African (AFR) AF: 0.00321 AC: 107 AN: 33286

American (AMR) AF: 0.00502 AC: 221 AN: 44032

Ashkenazi Jewish (ASJ) AF: 0.00482 AC: 125 AN: 25940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00115 AC: 98 AN: 85286

European-Finnish (FIN) AF: 0.00750 AC: 400 AN: 53346

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5748

European-Non Finnish (NFE) AF: 0.0263 AC: 29229 AN: 1110184

Other (OTH) AF: 0.0171 AC: 1031 AN: 60224

GnomAD4 genome AF: 0.0129 AC: 1964 AN: 152230 Hom.: 21 Cov.: 32 AF XY: 0.0118 AC XY: 879 AN XY: 74438

African (AFR) AF: 0.00412 AC: 171 AN: 41544

American (AMR) AF: 0.00661 AC: 101 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4818

European-Finnish (FIN) AF: 0.00736 AC: 78 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0232 AC: 1576 AN: 68010

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.0151 Hom.: 7

Bravo AF: 0.0129

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs146184583; hg19: chr3-57303548;