20-3471142-TGAG-T

Position:

• chr20-3471142-TGAG-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_139321.3(ATRN):​c.44_46del​(p.Arg15del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000295 in 1,356,190 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ATRN NM_139321.3 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.82

Genes affected

ATRN (HGNC:885): (attractin) This gene encodes both membrane-bound and secreted protein isoforms. A membrane-bound isoform exhibits sequence similarity with the mouse mahogany protein, a receptor involved in controlling obesity. A secreted isoform is involved in the initial immune cell clustering during inflammatory responses that may regulate the chemotactic activity of chemokines. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_139321.3. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRN	NM_139321.3	c.44_46del	p.Arg15del	inframe_deletion	1/29	ENST00000262919.10
ATRN	NM_001323332.2	c.44_46del	p.Arg15del	inframe_deletion	1/26
ATRN	NM_139322.4	c.44_46del	p.Arg15del	inframe_deletion	1/25
ATRN	NM_001207047.3	c.62+17_62+19del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRN	ENST00000262919.10	c.44_46del	p.Arg15del	inframe_deletion	1/29	5	NM_139321.3	P2
ATRN	ENST00000446916.2	c.44_46del	p.Arg15del	inframe_deletion	1/25	1		A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000295 AC: 4 AN: 1356190 Hom.: 0 AF XY: 0.00000149 AC XY: 1 AN XY: 669154

Gnomad4 AFR exome AF: 0.0000356

Gnomad4 AMR exome AF: 0.0000297

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 01, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with ATRN-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.44_46del, results in the deletion of 1 amino acid(s) of the ATRN protein (p.Arg15del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

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: rs1380172221; hg19: chr20-3451789;