7-92562348-C-G

Variant names:

• chr7-92562348-C-G
• rs1562886814
• NM_152789.4:c.678G>C

Variant summary

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

The NM_152789.4(FAM133B):​c.678G>C​(p.Lys226Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000724 in 1,380,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FAM133B NM_152789.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

Genes affected

FAM133B (HGNC:28629): (family with sequence similarity 133 member B) Enables RNA binding activity. [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=0.20804429).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM133B	NM_152789.4	c.678G>C	p.Lys226Asn	missense_variant	Exon 11 of 11	ENST00000445716.6	NP_690002.2
FAM133B	NM_001040057.3	c.648G>C	p.Lys216Asn	missense_variant	Exon 12 of 12		NP_001035146.1
FAM133B	NM_001288584.2	c.648G>C	p.Lys216Asn	missense_variant	Exon 11 of 11		NP_001275513.1
FAM133B	NR_109929.2	n.736G>C		non_coding_transcript_exon_variant	Exon 11 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM133B	ENST00000445716.6	c.678G>C	p.Lys226Asn	missense_variant	Exon 11 of 11	1	NM_152789.4	ENSP00000398401.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1380826 Hom.: 0 Cov.: 29 AF XY: 0.00000147 AC XY: 1 AN XY: 681376

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.678G>C (p.K226N) alteration is located in exon 11 (coding exon 11) of the FAM133B gene. This alteration results from a G to C substitution at nucleotide position 678, causing the lysine (K) at amino acid position 226 to be replaced by an asparagine (N). 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	0.86
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	.;T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.68	.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.062
Sift	Uncertain	0.013	D;D;D
Sift4G	Benign	0.18	T;T;T
Polyphen		0.45	.;B;.
Vest4		0.27
MutPred		0.22		.;Loss of methylation at K226 (P = 0.0023);.;
MVP		0.48
MPC		0.28
ClinPred		0.89	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.030

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

LitVar

Other links and lift over

dbSNP: rs1562886814; hg19: chr7-92191662;