chr15-49541745-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_152647.3(FAM227B):c.809C>T(p.Ser270Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000214 in 1,543,384 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 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
FAM227B
NM_152647.3 missense
NM_152647.3 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 4.65
Genes affected
FAM227B (HGNC:26543): (family with sequence similarity 227 member B)
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.904
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAM227B | NM_152647.3 | c.809C>T | p.Ser270Leu | missense_variant | 10/16 | ENST00000299338.11 | |
LOC105370811 | XR_001751537.2 | n.88+3284G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAM227B | ENST00000299338.11 | c.809C>T | p.Ser270Leu | missense_variant | 10/16 | 2 | NM_152647.3 | P1 | |
FAM227B | ENST00000561064.5 | c.707C>T | p.Ser236Leu | missense_variant | 9/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000230 AC: 5AN: 217204Hom.: 0 AF XY: 0.0000338 AC XY: 4AN XY: 118428
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GnomAD4 exome AF: 0.0000216 AC: 30AN: 1391266Hom.: 0 Cov.: 30 AF XY: 0.0000232 AC XY: 16AN XY: 690072
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152118Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74314
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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 | Apr 08, 2022 | The c.809C>T (p.S270L) alteration is located in exon 10 (coding exon 9) of the FAM227B gene. This alteration results from a C to T substitution at nucleotide position 809, causing the serine (S) at amino acid position 270 to be replaced by a leucine (L). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
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