2-61825355-A-G

Position:

• chr2-61825355-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001201543.2(FAM161A):​c.*1100T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 454,192 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0090 (4 hom., cov: 32)
  • Exomes 𝑓: 0.011 (32 hom.)
• Consequence: FAM161A NM_001201543.2 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.374

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-61825355-A-G is Benign according to our data. Variant chr2-61825355-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 336719.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00902 (1374/152266) while in subpopulation NFE AF= 0.0144 (979/68022). AF 95% confidence interval is 0.0136. There are 4 homozygotes in gnomad4. There are 621 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM161A	NM_001201543.2	c.*1100T>C		3_prime_UTR_variant	7/7	ENST00000404929.6	NP_001188472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM161A	ENST00000404929.6	c.*1100T>C		3_prime_UTR_variant	7/7	1	NM_001201543.2	ENSP00000385158	P1
FAM161A	ENST00000405894.3	c.*1100T>C		3_prime_UTR_variant	6/6	1		ENSP00000385893
FAM161A	ENST00000456262.5	c.*2598T>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000396105
FAM161A	ENST00000418113.5	c.*1723T>C		3_prime_UTR_variant, NMD_transcript_variant	8/8	5		ENSP00000416861

Frequencies

GnomAD3 genomes AF: 0.00904 AC: 1375 AN: 152148 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00258

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00892 AC: 1165 AN: 130616 Hom.: 7 AF XY: 0.00924 AC XY: 659 AN XY: 71296

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00571

Gnomad ASJ exome AF: 0.000987

Gnomad EAS exome AF: 0.00104

Gnomad SAS exome AF: 0.00907

Gnomad FIN exome AF: 0.0136

Gnomad NFE exome AF: 0.0137

Gnomad OTH exome AF: 0.00950

GnomAD4 exome AF: 0.0109 AC: 3300 AN: 301926 Hom.: 32 Cov.: 0 AF XY: 0.0109 AC XY: 1869 AN XY: 172068

Gnomad4 AFR exome AF: 0.00234

Gnomad4 AMR exome AF: 0.00539

Gnomad4 ASJ exome AF: 0.000927

Gnomad4 EAS exome AF: 0.000642

Gnomad4 SAS exome AF: 0.00964

Gnomad4 FIN exome AF: 0.0137

Gnomad4 NFE exome AF: 0.0140

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.00902 AC: 1374 AN: 152266 Hom.: 4 Cov.: 32 AF XY: 0.00834 AC XY: 621 AN XY: 74480

Gnomad4 AFR AF: 0.00258

Gnomad4 AMR AF: 0.00491

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.00621

Gnomad4 FIN AF: 0.0142

Gnomad4 NFE AF: 0.0144

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00955 Hom.: 6

Bravo AF: 0.00792

Asia WGS AF: 0.00405 AC: 15 AN: 3470

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Retinitis pigmentosa Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

FAM161A: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs78512710; hg19: chr2-62052490;