rs7588635
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_006343.3(MERTK):c.844G>A(p.Ala282Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00831 in 1,614,026 control chromosomes in the GnomAD database, including 939 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.043 ( 487 hom., cov: 32)
Exomes 𝑓: 0.0047 ( 452 hom. )
Consequence
MERTK
NM_006343.3 missense, splice_region
NM_006343.3 missense, splice_region
Scores
1
7
11
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 5.94
Genes affected
MERTK (HGNC:7027): (MER proto-oncogene, tyrosine kinase) This gene is a member of the MER/AXL/TYRO3 receptor kinase family and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) domains, and one tyrosine kinase domain. Mutations in this gene have been associated with disruption of the retinal pigment epithelium (RPE) phagocytosis pathway and onset of autosomal recessive retinitis pigmentosa (RP). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 2-111965277-G-A is Benign according to our data. Variant chr2-111965277-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 330749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MERTK | NM_006343.3 | c.844G>A | p.Ala282Thr | missense_variant, splice_region_variant | 5/19 | ENST00000295408.9 | NP_006334.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MERTK | ENST00000295408.9 | c.844G>A | p.Ala282Thr | missense_variant, splice_region_variant | 5/19 | 1 | NM_006343.3 | ENSP00000295408.4 | ||
MERTK | ENST00000439966.5 | n.*317G>A | splice_region_variant, non_coding_transcript_exon_variant | 5/19 | 1 | ENSP00000402129.1 | ||||
MERTK | ENST00000439966.5 | n.*317G>A | 3_prime_UTR_variant | 5/19 | 1 | ENSP00000402129.1 | ||||
MERTK | ENST00000409780.5 | c.316G>A | p.Ala106Thr | missense_variant, splice_region_variant | 4/18 | 5 | ENSP00000387277.1 |
Frequencies
GnomAD3 genomes AF: 0.0432 AC: 6578AN: 152126Hom.: 487 Cov.: 32
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GnomAD3 exomes AF: 0.0111 AC: 2791AN: 251316Hom.: 188 AF XY: 0.00812 AC XY: 1103AN XY: 135830
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GnomAD4 exome AF: 0.00467 AC: 6825AN: 1461782Hom.: 452 Cov.: 30 AF XY: 0.00410 AC XY: 2978AN XY: 727194
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GnomAD4 genome AF: 0.0433 AC: 6589AN: 152244Hom.: 487 Cov.: 32 AF XY: 0.0418 AC XY: 3112AN XY: 74438
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Retinitis pigmentosa 38 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Retinitis pigmentosa Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;T
Polyphen
B;B;.
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at