11-126256654-T-C

Variant names:

• chr11-126256654-T-C
• NM_024556.4:c.784T>C

Variant summary

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

The NM_024556.4(FAM118B):​c.784T>C​(p.Phe262Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.82

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]

SRPRA (HGNC:11307): (SRP receptor subunit alpha) The gene encodes a subunit of the endoplasmic reticulum signal recognition particle receptor that, in conjunction with the signal recognition particle, is involved in the targeting and translocation of signal sequence tagged secretory and membrane proteins across the endoplasmic reticulum. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM118B	NM_024556.4	c.784T>C	p.Phe262Leu	missense_variant	Exon 7 of 9	ENST00000533050.6	NP_078832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM118B	ENST00000533050.6	c.784T>C	p.Phe262Leu	missense_variant	Exon 7 of 9	1	NM_024556.4	ENSP00000433343.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.784T>C (p.F262L) alteration is located in exon 7 (coding exon 5) of the FAM118B gene. This alteration results from a T to C substitution at nucleotide position 784, causing the phenylalanine (F) at amino acid position 262 to be replaced by a leucine (L). 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	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T;T;T;T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;.;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.70	D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;.;.;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.4	N;.;N;N;N;D
REVEL	Benign	0.27
Sift	Benign	0.17	T;.;T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.98	D;P;D;P;.;.
Vest4		0.80
MutPred		0.72		Loss of methylation at K267 (P = 0.0748);.;Loss of methylation at K267 (P = 0.0748);.;Loss of methylation at K267 (P = 0.0748);.;
MVP		0.67
MPC		0.85
ClinPred		0.90	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.72

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: chr11-126126549;