chr20-56533430-G-T

Position:

• chr20-56533430-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013646.4(FAM209B):​c.89G>T​(p.Ser30Ile) 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. 13/21 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: -0.500

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.108057916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM209B	NM_001013646.4	c.89G>T	p.Ser30Ile	missense_variant	1/2	ENST00000371325.1	NP_001013668.2
FAM209A	XM_047439964.1	c.*230G>T		3_prime_UTR_variant	5/5		XP_047295920.1
FAM209A	XM_047439965.1	c.*383G>T		3_prime_UTR_variant	6/6		XP_047295921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM209B	ENST00000371325.1	c.89G>T	p.Ser30Ile	missense_variant	1/2	1	NM_001013646.4	ENSP00000360376.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 21, 2022

The c.89G>T (p.S30I) alteration is located in exon 1 (coding exon 1) of the FAM209B gene. This alteration results from a G to T substitution at nucleotide position 89, causing the serine (S) at amino acid position 30 to be replaced by an isoleucine (I). 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	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0059	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.011
Sift	Benign	0.15	T
Sift4G	Benign	0.18	T
Polyphen		0.53	P
Vest4		0.20
MutPred		0.29		Loss of disorder (P = 0.0128);
MVP		0.13
MPC		1.1
ClinPred		0.23	T
GERP RS		0.33
Varity_R		0.084
gMVP		0.087

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: chr20-55108486; COSMIC: COSV100991025;