chr2-61840157-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001201543.2(FAM161A):​c.847C>G​(p.Arg283Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R283Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

FAM161A
NM_001201543.2 missense

Scores

9
6
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.10
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAM161ANM_001201543.2 linkuse as main transcriptc.847C>G p.Arg283Gly missense_variant 3/7 ENST00000404929.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAM161AENST00000404929.6 linkuse as main transcriptc.847C>G p.Arg283Gly missense_variant 3/71 NM_001201543.2 P1Q3B820-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000414
AC:
5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.65
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.096
.;T
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.98
D;D
MetaSVM
Benign
-0.59
T
MutationAssessor
Pathogenic
2.9
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.42
T
PROVEAN
Pathogenic
-6.1
D;D
REVEL
Uncertain
0.42
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.012
D;D
Polyphen
1.0
D;D
Vest4
0.82
MutPred
0.91
Gain of ubiquitination at K280 (P = 0.0395);Gain of ubiquitination at K280 (P = 0.0395);
MVP
0.71
MPC
0.30
ClinPred
1.0
D
GERP RS
5.3
Varity_R
0.84
gMVP
0.41

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.

Other links and lift over

dbSNP: rs748847284; hg19: chr2-62067292; API