chr11-47588213-C-T

Variant names:

• chr11-47588213-C-T
• NM_001164379.3:c.331C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.780

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]

ACMG classification

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
FAM180B	NM_001164379.3	c.331C>T	p.Pro111Ser	missense_variant	Exon 3 of 3	ENST00000538490.3	NP_001157851.1
FAM180B	NM_001367966.1	c.295C>T	p.Pro99Ser	missense_variant	Exon 2 of 2		NP_001354895.1
FAM180B	NM_001367967.1	c.181C>T	p.Pro61Ser	missense_variant	Exon 2 of 2		NP_001354896.1
FAM180B	NM_001367968.1	c.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
FAM180B	ENST00000538490.3	c.331C>T	p.Pro111Ser	missense_variant	Exon 3 of 3	1	NM_001164379.3	ENSP00000443133.2

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

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;