2-61825319-C-A

Variant names:

• chr2-61825319-C-A
• rs191936453
• ENST00000456262.5:n.*2634G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000456262.5(FAM161A):​n.*2634G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000865 in 454,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00082 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (0 hom.)
• Consequence: FAM161A ENST00000456262.5 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.993
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM161A	NM_001201543.2	c.*1136G>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000404929.6	NP_001188472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM161A	ENST00000404929.6	c.*1136G>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001201543.2	ENSP00000385158.1

Frequencies

GnomAD3 genomes AF: 0.000822 AC: 125 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000704 AC: 92 AN: 130622 AF XY: 0.000799

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000903

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.00175

GnomAD4 exome AF: 0.000888 AC: 268 AN: 301926 Hom.: 0 Cov.: 0 AF XY: 0.000941 AC XY: 162 AN XY: 172066

African (AFR) AF: 0.000117 AC: 1 AN: 8554

American (AMR) AF: 0.00117 AC: 32 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10786

East Asian (EAS) AF: 0.00 AC: 0 AN: 9346

South Asian (SAS) AF: 0.000117 AC: 7 AN: 59650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12364

Middle Eastern (MID) AF: 0.00174 AC: 2 AN: 1150

European-Non Finnish (NFE) AF: 0.00139 AC: 221 AN: 158762

Other (OTH) AF: 0.000356 AC: 5 AN: 14040

GnomAD4 genome AF: 0.000821 AC: 125 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.000699 AC XY: 52 AN XY: 74406

African (AFR) AF: 0.000217 AC: 9 AN: 41524

American (AMR) AF: 0.000851 AC: 13 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

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

European-Non Finnish (NFE) AF: 0.00150 AC: 102 AN: 68020

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000682 Hom.: 0

Bravo AF: 0.000861

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-0.99

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

Other links and lift over

dbSNP: rs191936453; hg19: chr2-62052454;