chr20-56536273-C-A

Variant names:

• chr20-56536273-C-A
• NM_001013646.4:c.351C>A

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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: FAM209B NM_001013646.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.273
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06586805).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013646.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM209B	NM_001013646.4	MANE Select	c.351C>A	p.Asn117Lys	missense	Exon 2 of 2	NP_001013668.2	Q5JX69

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM209B	ENST00000371325.1	TSL:1 MANE Select	c.351C>A	p.Asn117Lys	missense	Exon 2 of 2	ENSP00000360376.1	Q5JX69

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.27
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
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chr20-55111329;