ENST00000456262.5:n.*2598T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000456262.5(FAM161A):n.*2598T>C 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 0.0103 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
ENST00000456262.5 non_coding_transcript_exon

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.374

Publications

1 publications found

Variant links:

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

FAM161A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM161A	NM_001201543.2 link	c.*1100T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000404929.6	NP_001188472.1	Q3B820-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM161A	ENST00000404929.6 link	c.*1100T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_001201543.2	ENSP00000385158.1		Q3B820-3

Frequencies

GnomAD3 genomes

AF:

0.00904

AC:

1375

AN:

152148

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00892

AC:

1165

AN:

130616

AF XY:

0.00924

show subpopulations

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 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.:

Cov.:

AF XY:

0.0109

AC XY:

1869

AN XY:

172068

show subpopulations

African (AFR)

AF:

0.00234

AC:

AN:

8554

American (AMR)

AF:

0.00539

AC:

147

AN:

27272

Ashkenazi Jewish (ASJ)

AF:

0.000927

AC:

AN:

10786

East Asian (EAS)

AF:

0.000642

AC:

AN:

9348

South Asian (SAS)

AF:

0.00964

AC:

575

AN:

59650

European-Finnish (FIN)

AF:

0.0137

AC:

169

AN:

12364

Middle Eastern (MID)

AF:

0.00435

AC:

AN:

1150

European-Non Finnish (NFE)

AF:

0.0140

AC:

2216

AN:

158760

Other (OTH)

AF:

0.0108

AC:

152

AN:

14042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

202

404

605

807

1009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00902

AC:

1374

AN:

152266

Hom.:

Cov.:

AF XY:

0.00834

AC XY:

621

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00258

AC:

107

AN:

41550

American (AMR)

AF:

0.00491

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.00621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0142

AC:

151

AN:

10610

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0144

AC:

979

AN:

68022

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

161

241

322

402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00955

Hom.:

Bravo

AF:

0.00792

Asia WGS

AF:

0.00405

AC:

AN:

3470

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Retinitis pigmentosa

Uncertain:1

Jan 12, 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. -

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FAM161A: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.0

(source)

DANN

Benign

0.71

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism

(source)

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

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ENST00000456262.5:n.*2598T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over