rs932298235

Variant names:

• chr7-92577155-C-T
• rs932298235
• NM_152789.4:c.413G>A

Variant summary

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

The NM_152789.4(FAM133B):​c.413G>A​(p.Arg138His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,495,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: FAM133B NM_152789.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

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

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=0.09490761).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152789.4. 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
	FAM133B	NM_152789.4	MANE Select	c.413G>A	p.Arg138His	missense	Exon 7 of 11	NP_690002.2	Q5BKY9-1
	FAM133B	NM_001040057.3		c.383G>A	p.Arg128His	missense	Exon 8 of 12	NP_001035146.1	Q5BKY9-2
	FAM133B	NM_001288584.2		c.383G>A	p.Arg128His	missense	Exon 7 of 11	NP_001275513.1	Q5BKY9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM133B	ENST00000445716.6	TSL:1 MANE Select	c.413G>A	p.Arg138His	missense	Exon 7 of 11	ENSP00000398401.1	Q5BKY9-1
	FAM133B	ENST00000427372.5	TSL:1	c.383G>A	p.Arg128His	missense	Exon 7 of 11	ENSP00000402843.1	Q5BKY9-2
	FAM133B	ENST00000438306.5	TSL:1	c.383G>A	p.Arg128His	missense	Exon 8 of 12	ENSP00000389783.1	Q5BKY9-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151994 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000762 AC: 1 AN: 131206 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000238 AC: 32 AN: 1343682 Hom.: 0 Cov.: 28 AF XY: 0.0000197 AC XY: 13 AN XY: 661020

African (AFR) AF: 0.00 AC: 0 AN: 29468

American (AMR) AF: 0.00 AC: 0 AN: 29810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24018

East Asian (EAS) AF: 0.00 AC: 0 AN: 33456

South Asian (SAS) AF: 0.0000298 AC: 2 AN: 67196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5196

European-Non Finnish (NFE) AF: 0.0000266 AC: 28 AN: 1051784

Other (OTH) AF: 0.0000362 AC: 2 AN: 55250

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151994 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74248

African (AFR) AF: 0.00 AC: 0 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000612 Hom.: 0

Bravo AF: 0.0000151

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	0.070
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.094
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.047
Sift	Benign	0.46	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.14
MVP		0.24
MPC		0.29
ClinPred		0.45	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.016
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs932298235; hg19: chr7-92206469; COSMIC: COSV101300239; COSMIC: COSV101300239;