2-45389443-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_018079.5(SRBD1):āc.2855C>Gā(p.Thr952Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,796 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 (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
SRBD1
NM_018079.5 missense
NM_018079.5 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 9.15
Genes affected
Genome browser will be placed here
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, 0.746
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SRBD1 | NM_018079.5 | c.2855C>G | p.Thr952Arg | missense_variant | 21/21 | ENST00000263736.5 | NP_060549.4 | |
SRBD1 | XM_011532946.3 | c.2807C>G | p.Thr936Arg | missense_variant | 21/21 | XP_011531248.1 | ||
SRBD1 | XM_047444861.1 | c.1412C>G | p.Thr471Arg | missense_variant | 13/13 | XP_047300817.1 | ||
SRBD1 | XM_047444862.1 | c.1412C>G | p.Thr471Arg | missense_variant | 12/12 | XP_047300818.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SRBD1 | ENST00000263736.5 | c.2855C>G | p.Thr952Arg | missense_variant | 21/21 | 2 | NM_018079.5 | ENSP00000263736 | P1 | |
SRBD1 | ENST00000490133.5 | n.1752C>G | non_coding_transcript_exon_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461796Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727190
GnomAD4 exome
AF:
AC:
1
AN:
1461796
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
727190
Gnomad4 AFR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
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 | Jun 17, 2024 | The c.2855C>G (p.T952R) alteration is located in exon 21 (coding exon 20) of the SRBD1 gene. This alteration results from a C to G substitution at nucleotide position 2855, causing the threonine (T) at amino acid position 952 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of MoRF binding (P = 0.0241);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at