rs558080743

Variant names:

• chr2-61826479-CTCT-C
• rs558080743
• NM_001201543.2:c.2124_2126delAGA

Your query was ambiguous. Multiple possible variants found:

• chr2-61826479-CTCT-C
• chr2-61826479-CTCT-CTCTTCT

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_001201543.2(FAM161A):​c.2124_2126delAGA​(p.Glu709del) variant causes a disruptive 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 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:4
• Conservation: PhyloP100: 0.712
• Publications: 0 publications found

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]

FAM161A Gene-Disease associations (from GenCC):

• retinitis pigmentosa 28

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -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 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201543.2. 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
	FAM161A	NM_001201543.2	MANE Select	c.2124_2126delAGA	p.Glu709del	disruptive_inframe_deletion	Exon 7 of 7	NP_001188472.1	Q3B820-3
	FAM161A	NM_032180.3		c.1956_1958delAGA	p.Glu653del	disruptive_inframe_deletion	Exon 6 of 6	NP_115556.2	Q3B820-1
	FAM161A	NR_037710.2		n.1919_1921delAGA		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM161A	ENST00000404929.6	TSL:1 MANE Select	c.2124_2126delAGA	p.Glu709del	disruptive_inframe_deletion	Exon 7 of 7	ENSP00000385158.1	Q3B820-3
	FAM161A	ENST00000405894.3	TSL:1	c.1956_1958delAGA	p.Glu653del	disruptive_inframe_deletion	Exon 6 of 6	ENSP00000385893.3	Q3B820-1
	FAM161A	ENST00000456262.5	TSL:1	n.*1471_*1473delAGA		non_coding_transcript_exon	Exon 6 of 6	ENSP00000396105.1	F8WCZ8

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

GnomAD2 exomes AF: 0.000449 AC: 109 AN: 242832 AF XY: 0.000494

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 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

African (AFR) AF: 0.000269 AC: 9 AN: 33436

American (AMR) AF: 0.000474 AC: 21 AN: 44278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85580

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00115 AC: 1272 AN: 1109746

Other (OTH) AF: 0.000730 AC: 44 AN: 60268

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

African (AFR) AF: 0.000240 AC: 10 AN: 41594

American (AMR) AF: 0.00203 AC: 31 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00110 AC: 75 AN: 68026

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000215 Hom.: 0

Bravo AF: 0.000918

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	Retinal dystrophy (1)
-	1	-	Retinitis pigmentosa (1)
-	1	-	Retinitis pigmentosa 28 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.71
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs558080743; hg19: chr2-62053614;