20-3471319-C-CGCT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_139321.3(ATRN):c.230_232dup(p.Leu77dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000466 in 1,481,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: ATRN NM_139321.3 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

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 Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_139321.3
• BS2: High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATRN	NM_139321.3	c.230_232dup	p.Leu77dup	inframe_insertion	1/29	ENST00000262919.10
ATRN	NM_001323332.2	c.230_232dup	p.Leu77dup	inframe_insertion	1/26
ATRN	NM_139322.4	c.230_232dup	p.Leu77dup	inframe_insertion	1/25
ATRN	NM_001207047.3	c.62+203_62+205dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATRN	ENST00000262919.10	c.230_232dup	p.Leu77dup	inframe_insertion	1/29	5	NM_139321.3	P2
ATRN	ENST00000446916.2	c.230_232dup	p.Leu77dup	inframe_insertion	1/25	1		A2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152068 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000587 AC: 4 AN: 68158 Hom.: 0 AF XY: 0.0000765 AC XY: 3 AN XY: 39226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000148

Gnomad ASJ exome AF: 0.000192

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000399

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000459 AC: 61 AN: 1329038 Hom.: 0 Cov.: 32 AF XY: 0.0000550 AC XY: 36 AN XY: 655008

Gnomad4 AFR exome AF: 0.0000749

Gnomad4 AMR exome AF: 0.000147

Gnomad4 ASJ exome AF: 0.0000869

Gnomad4 EAS exome AF: 0.0000338

Gnomad4 SAS exome AF: 0.0000276

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000445

Gnomad4 OTH exome AF: 0.0000543

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74396

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000583

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

Invitae

Jan 24, 2024

This variant, c.230_232dup, results in the insertion of 1 amino acid(s) of the ATRN protein (p.Leu77dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs773492637, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with ATRN-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs772463780; hg19: chr20-3451966;