11-47588273-C-T

Variant names:

• chr11-47588273-C-T
• rs2097272828
• NM_001164379.3:c.391C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164379.3(FAM180B):​c.391C>T​(p.Arg131Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000433 in 1,384,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: FAM180B NM_001164379.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30386782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM180B	NM_001164379.3	c.391C>T	p.Arg131Trp	missense_variant	Exon 3 of 3	ENST00000538490.3	NP_001157851.1
FAM180B	NM_001367966.1	c.355C>T	p.Arg119Trp	missense_variant	Exon 2 of 2		NP_001354895.1
FAM180B	NM_001367967.1	c.241C>T	p.Arg81Trp	missense_variant	Exon 2 of 2		NP_001354896.1
FAM180B	NM_001367968.1	c.205C>T	p.Arg69Trp	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.391C>T	p.Arg131Trp	missense_variant	Exon 3 of 3	1	NM_001164379.3	ENSP00000443133.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000433 AC: 6 AN: 1384918 Hom.: 0 Cov.: 31 AF XY: 0.00000439 AC XY: 3 AN XY: 683392

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000560

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.391C>T (p.R131W) 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 391, causing the arginine (R) at amino acid position 131 to be replaced by a tryptophan (W). 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	0.14
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Vest4		0.40
MVP		0.25
ClinPred		0.98	D
GERP RS		4.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2097272828; hg19: chr11-47609825;