2-61826479-CTCT-C

Position:

• chr2-61826479-CTCT-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_001201543.2(FAM161A):​c.2124_2126del​(p.Glu709del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000921 in 1,610,376 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00079 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (2 hom.)
• Consequence: FAM161A NM_001201543.2 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.712

Genes affected

FAM161A (HGNC:25808): (FAM161 centrosomal protein A) This gene belongs to the FAM161 family. It is expressed mainly in the retina. Mouse studies suggested that this gene is involved in development of retinal progenitors during embryogenesis, and that its activity is restricted to mature photoreceptors after birth. Mutations in this gene cause autosomal recessive retinitis pigmentosa-28. Alternatively spliced transcript variants have been identified.[provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001201543.2. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM161A	NM_001201543.2	c.2124_2126del	p.Glu709del	inframe_deletion	7/7	ENST00000404929.6	NP_001188472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM161A	ENST00000404929.6	c.2124_2126del	p.Glu709del	inframe_deletion	7/7	1	NM_001201543.2	ENSP00000385158	P1
FAM161A	ENST00000405894.3	c.1956_1958del	p.Glu653del	inframe_deletion	6/6	1		ENSP00000385893
FAM161A	ENST00000456262.5	c.*1471_*1473del		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000396105
FAM161A	ENST00000418113.5	c.*596_*598del		3_prime_UTR_variant, NMD_transcript_variant	8/8	5		ENSP00000416861

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 121 AN: 152230 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00110

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000449 AC: 109 AN: 242832 Hom.: 0 AF XY: 0.000494 AC XY: 65 AN XY: 131552

Gnomad AFR exome AF: 0.000133

Gnomad AMR exome AF: 0.000295

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000101

Gnomad FIN exome AF: 0.0000469

Gnomad NFE exome AF: 0.000787

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.000934 AC: 1362 AN: 1458028 Hom.: 2 AF XY: 0.000913 AC XY: 662 AN XY: 724930

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000474

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.00115

Gnomad4 OTH exome AF: 0.000730

GnomAD4 genome AF: 0.000794 AC: 121 AN: 152348 Hom.: 2 Cov.: 32 AF XY: 0.000752 AC XY: 56 AN XY: 74492

Gnomad4 AFR AF: 0.000240

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00110

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000215 Hom.: 0

Bravo AF: 0.000918

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Retinitis pigmentosa 28 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Counsyl

Sep 19, 2017

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 28, 2022

This variant, c.2124_2126del, results in the deletion of 1 amino acid(s) of the FAM161A protein (p.Glu709del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs558080743, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with FAM161A-related conditions. ClinVar contains an entry for this variant (Variation ID: 553904). 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. -

Retinitis pigmentosa Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs558080743; hg19: chr2-62053614;