chr11-47588213-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164379.3(FAM180B):​c.331C>T​(p.Pro111Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

FAM180B
NM_001164379.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.780
Variant links:
Genes affected
FAM180B (HGNC:34451): (family with sequence similarity 180 member B) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0867199).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM180BNM_001164379.3 linkc.331C>T p.Pro111Ser missense_variant Exon 3 of 3 ENST00000538490.3 NP_001157851.1 Q6P0A1
FAM180BNM_001367966.1 linkc.295C>T p.Pro99Ser missense_variant Exon 2 of 2 NP_001354895.1
FAM180BNM_001367967.1 linkc.181C>T p.Pro61Ser missense_variant Exon 2 of 2 NP_001354896.1
FAM180BNM_001367968.1 linkc.145C>T p.Pro49Ser missense_variant Exon 3 of 3 NP_001354897.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM180BENST00000538490.3 linkc.331C>T p.Pro111Ser missense_variant Exon 3 of 3 1 NM_001164379.3 ENSP00000443133.2 Q6P0A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.331C>T (p.P111S) alteration is located in exon 3 (coding exon 3) of the FAM180B gene. This alteration results from a C to T substitution at nucleotide position 331, causing the proline (P) at amino acid position 111 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.012
T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.083
FATHMM_MKL
Benign
0.69
D
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.087
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.040
Sift
Benign
0.11
T
Sift4G
Benign
0.29
T
Vest4
0.070
MVP
0.048
ClinPred
0.79
D
GERP RS
4.3

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47609765; API