20-56533507-C-G

Variant names:

• chr20-56533507-C-G
• NM_001013646.4:c.166C>G

Variant summary

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

The NM_001013646.4(FAM209B):​c.166C>G​(p.Leu56Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM209B NM_001013646.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54

Genes affected

FAM209B (HGNC:16101): (family with sequence similarity 209 member B) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM209A (HGNC:16100): (family with sequence similarity 209 member A) Located in extracellular exosome and nucleus. [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=0.3461691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM209B	NM_001013646.4	c.166C>G	p.Leu56Val	missense_variant	Exon 1 of 2	ENST00000371325.1	NP_001013668.2
FAM209A	XM_047439964.1	c.*307C>G		3_prime_UTR_variant	Exon 5 of 5		XP_047295920.1
FAM209A	XM_047439965.1	c.*460C>G		3_prime_UTR_variant	Exon 6 of 6		XP_047295921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM209B	ENST00000371325.1	c.166C>G	p.Leu56Val	missense_variant	Exon 1 of 2	1	NM_001013646.4	ENSP00000360376.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.166C>G (p.L56V) alteration is located in exon 1 (coding exon 1) of the FAM209B gene. This alteration results from a C to G substitution at nucleotide position 166, causing the leucine (L) at amino acid position 56 to be replaced by a valine (V). 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	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.075
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.36
MutPred		0.18		Loss of helix (P = 0.0444);
MVP		0.49
MPC		1.4
ClinPred		0.93	D
GERP RS		1.8
Varity_R		0.20
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-55108563;