2-61825639-CTTTTTTT-CTTTT

Variant names:

• chr2-61825639-CTTT-C
• rs759062810
• ENST00000456262.5:n.*2311_*2313delAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001201543.2(FAM161A):​c.*813_*815delAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000816 in 397,162 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: FAM161A NM_001201543.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM161A	NM_001201543.2	c.*813_*815delAAA		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.*813_*815delAAA		3_prime_UTR_variant	Exon 7 of 7	1	NM_001201543.2	ENSP00000385158.1

Frequencies

GnomAD3 genomes AF: 0.0000212 AC: 3 AN: 141758 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00326 AC: 166 AN: 50930 AF XY: 0.00374

Gnomad AFR exome AF: 0.00250

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.00383

Gnomad EAS exome AF: 0.000818

Gnomad FIN exome AF: 0.00603

Gnomad NFE exome AF: 0.00351

Gnomad OTH exome AF: 0.00263

GnomAD4 exome AF: 0.00126 AC: 321 AN: 255404 Hom.: 0 AF XY: 0.00135 AC XY: 198 AN XY: 147056

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000687 AC: 4 AN: 5822

American (AMR) AF: 0.00250 AC: 42 AN: 16810

Ashkenazi Jewish (ASJ) AF: 0.00265 AC: 23 AN: 8686

East Asian (EAS) AF: 0.000114 AC: 1 AN: 8788

South Asian (SAS) AF: 0.00128 AC: 63 AN: 49386

European-Finnish (FIN) AF: 0.00123 AC: 13 AN: 10552

Middle Eastern (MID) AF: 0.00348 AC: 3 AN: 862

European-Non Finnish (NFE) AF: 0.00108 AC: 154 AN: 142628

Other (OTH) AF: 0.00152 AC: 18 AN: 11870

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000212 AC: 3 AN: 141758 Hom.: 0 Cov.: 31 AF XY: 0.0000291 AC XY: 2 AN XY: 68682

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000257 AC: 1 AN: 38948

American (AMR) AF: 0.00 AC: 0 AN: 14060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3344

East Asian (EAS) AF: 0.00 AC: 0 AN: 4962

South Asian (SAS) AF: 0.00 AC: 0 AN: 4466

European-Finnish (FIN) AF: 0.000236 AC: 2 AN: 8464

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64440

Other (OTH) AF: 0.00 AC: 0 AN: 1886

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00207 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

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: rs759062810; hg19: chr2-62052774;