20-56536273-C-A

Position:

• chr20-56536273-C-A

Variant summary

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

The NM_001013646.4(FAM209B):​c.351C>A​(p.Asn117Lys) 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. 15/21 in silico tools predict 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: 0.273

Genes affected

FAM209B (HGNC:16101): (family with sequence similarity 209 member B) Located in nucleus. [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=0.06586805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM209B	NM_001013646.4	c.351C>A	p.Asn117Lys	missense_variant	2/2	ENST00000371325.1	NP_001013668.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM209B	ENST00000371325.1	c.351C>A	p.Asn117Lys	missense_variant	2/2	1	NM_001013646.4	ENSP00000360376.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.351C>A (p.N117K) alteration is located in exon 2 (coding exon 2) of the FAM209B gene. This alteration results from a C to A substitution at nucleotide position 351, causing the asparagine (N) at amino acid position 117 to be replaced by a lysine (K). 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	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.2
DANN	Benign	0.94
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.0090
Sift	Benign	0.040	D
Sift4G	Benign	0.41	T
Polyphen		0.15	B
Vest4		0.16
MutPred		0.29		Gain of ubiquitination at N117 (P = 0.0185);
MVP		0.048
MPC		0.59
ClinPred		0.16	T
GERP RS		2.4
Varity_R		0.081
gMVP		0.27

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: chr20-55111329;