11-47587802-C-A

Variant names:

• chr11-47587802-C-A
• rs906193622
• NM_001164379.3:c.137C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001164379.3(FAM180B):​c.137C>A​(p.Ala46Asp) 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. 14/16 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM180B NM_001164379.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.98

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046851307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM180B	NM_001164379.3	c.137C>A	p.Ala46Asp	missense_variant	Exon 2 of 3	ENST00000538490.3	NP_001157851.1
FAM180B	NM_001367968.1	c.-85C>A		5_prime_UTR_variant	Exon 2 of 3		NP_001354897.1
FAM180B	NM_001367966.1	c.86-202C>A		intron_variant	Intron 1 of 1		NP_001354895.1
FAM180B	NM_001367967.1	c.7-237C>A		intron_variant	Intron 1 of 1		NP_001354896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM180B	ENST00000538490.3	c.137C>A	p.Ala46Asp	missense_variant	Exon 2 of 3	1	NM_001164379.3	ENSP00000443133.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1382832 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682290

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Mar 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.137C>A (p.A46D) alteration is located in exon 2 (coding exon 2) of the FAM180B gene. This alteration results from a C to A substitution at nucleotide position 137, causing the alanine (A) at amino acid position 46 to be replaced by an aspartic acid (D). 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	0.083
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.079	N
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.8	N
REVEL	Benign	0.055
Sift	Benign	0.43	T
Sift4G	Benign	0.55	T
Vest4		0.25
MVP		0.048
ClinPred		0.069	T
GERP RS		-1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs906193622; hg19: chr11-47609354;