11-126235083-C-T

Variant names:

• chr11-126235083-C-T
• rs774217069
• NM_024556.4:c.82C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024556.4(FAM118B):​c.82C>T​(p.Pro28Ser) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM118B NM_024556.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54
• Publications: 0 publications found

Genes affected

FAM118B (HGNC:26110): (family with sequence similarity 118 member B) Enables identical protein binding activity. Predicted to be involved in Cajal body organization. Predicted to be located in Cajal body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1525782).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024556.4. 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
	FAM118B	NM_024556.4	MANE Select	c.82C>T	p.Pro28Ser	missense	Exon 3 of 9	NP_078832.1	Q9BPY3
	FAM118B	NM_001439324.1		c.82C>T	p.Pro28Ser	missense	Exon 2 of 8	NP_001426253.1
	FAM118B	NM_001330446.2		c.82C>T	p.Pro28Ser	missense	Exon 3 of 9	NP_001317375.1	J3KP39

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM118B	ENST00000533050.6	TSL:1 MANE Select	c.82C>T	p.Pro28Ser	missense	Exon 3 of 9	ENSP00000433343.1	Q9BPY3
	FAM118B	ENST00000891485.1		c.82C>T	p.Pro28Ser	missense	Exon 3 of 10	ENSP00000561544.1
	FAM118B	ENST00000891481.1		c.82C>T	p.Pro28Ser	missense	Exon 3 of 9	ENSP00000561540.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

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	0.21
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.080
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.66	N
PhyloP100		3.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.25
Sift	Benign	0.53	T
Sift4G	Benign	0.81	T
Polyphen		0.27	B
Vest4		0.42
MutPred		0.17		Gain of phosphorylation at P28 (P = 0.0115)
MVP		0.48
MPC		0.21
ClinPred		0.30	T
GERP RS		6.2
Varity_R		0.087
gMVP		0.59
Mutation Taster		=51/49	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

dbSNP: rs774217069; hg19: chr11-126104978;