2-45477060-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_018079.5(SRBD1):c.1982G>A(p.Arg661His) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,613,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
SRBD1
NM_018079.5 missense
NM_018079.5 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 6.50
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.824
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SRBD1 | NM_018079.5 | c.1982G>A | p.Arg661His | missense_variant | 16/21 | ENST00000263736.5 | NP_060549.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SRBD1 | ENST00000263736.5 | c.1982G>A | p.Arg661His | missense_variant | 16/21 | 2 | NM_018079.5 | ENSP00000263736 | P1 | |
SRBD1 | ENST00000475073.5 | n.373+11180G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250714Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135526
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461242Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 726910
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74312
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2023 | The c.1982G>A (p.R661H) alteration is located in exon 16 (coding exon 15) of the SRBD1 gene. This alteration results from a G to A substitution at nucleotide position 1982, causing the arginine (R) at amino acid position 661 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at