2-131055566-C-A

Variant names:

• chr2-131055566-C-A
• NM_001009993.4:c.284G>T

Variant summary

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

The NM_001009993.4(FAM168B):​c.284G>T​(p.Ser95Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM168B NM_001009993.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

Genes affected

FAM168B (HGNC:27016): (family with sequence similarity 168 member B) Located in extracellular exosome. [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=0.2163746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM168B	NM_001009993.4	c.284G>T	p.Ser95Ile	missense_variant	Exon 4 of 7	ENST00000389915.4	NP_001009993.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM168B	ENST00000389915.4	c.284G>T	p.Ser95Ile	missense_variant	Exon 4 of 7	3	NM_001009993.4	ENSP00000374565.3
FAM168B	ENST00000409185.5	c.284G>T	p.Ser95Ile	missense_variant	Exon 4 of 7	1		ENSP00000387051.1

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

Apr 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.284G>T (p.S95I) alteration is located in exon 4 (coding exon 3) of the FAM168B gene. This alteration results from a G to T substitution at nucleotide position 284, causing the serine (S) at amino acid position 95 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	0.051
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.079	T;T
Polyphen		0.26	B;B
Vest4		0.48
MutPred		0.34		Loss of glycosylation at S95 (P = 0.0069);Loss of glycosylation at S95 (P = 0.0069);
MVP		0.19
MPC		0.90
ClinPred		0.78	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.51

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: chr2-131813139;