2-61842223-T-C

Position:

chr2-61842223-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001201543.2(FAM161A):c.321A>G(p.Ile107Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,612,636 control chromosomes in the GnomAD database, including 28,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2167 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26175 hom. )

Consequence

FAM161A
NM_001201543.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.41

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012713075).

BP6

Variant 2-61842223-T-C is Benign according to our data. Variant chr2-61842223-T-C is described in ClinVar as [Benign]. Clinvar id is 336744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-61842223-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM161A	NM_001201543.2 linkuse as main transcript	c.321A>G	p.Ile107Met	missense_variant	2/7	ENST00000404929.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM161A	ENST00000404929.6 linkuse as main transcript	c.321A>G	p.Ile107Met	missense_variant	2/7	1	NM_001201543.2	P1	Q3B820-3

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24937

AN:

152084

Hom.:

2172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.182

AC:

45380

AN:

249384

Hom.:

4305

AF XY:

0.182

AC XY:

24638

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.177

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.188

AC:

274156

AN:

1460434

Hom.:

26175

Cov.:

AF XY:

0.187

AC XY:

136033

AN XY:

726616

show subpopulations

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.155

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.164

AC:

24933

AN:

152202

Hom.:

2167

Cov.:

AF XY:

0.162

AC XY:

12069

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.183

Hom.:

6632

Bravo

AF:

0.166

TwinsUK

AF:

0.194

AC:

718

ALSPAC

AF:

0.195

AC:

752

ESP6500AA

AF:

0.127

AC:

466

ESP6500EA

AF:

0.186

AC:

1522

ExAC

AF:

0.183

AC:

22054

Asia WGS

AF:

0.194

AC:

674

AN:

3478

EpiCase

AF:

0.184

EpiControl

AF:

0.194

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinitis pigmentosa 28

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Retinitis pigmentosa

Benign:1

Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.7

DANN

Benign

0.71

DEOGEN2

Benign

0.00031

.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.58

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.21

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.081

Sift

Benign

0.30

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.017

B;B

Vest4

0.017

MPC

0.038

ClinPred

0.00064

GERP RS

1.7

Varity_R

0.057

gMVP

0.086

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over