10-124681841-G-C

Variant names:

• chr10-124681841-G-C
• rs754765742
• NM_014661.4:c.672C>G

Variant summary

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

The NM_014661.4(FAM53B):​c.672C>G​(p.Asp224Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,124 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM53B NM_014661.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.172
• Publications: 0 publications found

Genes affected

FAM53B (HGNC:28968): (family with sequence similarity 53 member B) Involved in positive regulation of canonical Wnt signaling pathway. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258539 (HGNC:):

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=0.13520855).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014661.4. 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
	FAM53B	NM_014661.4	MANE Select	c.672C>G	p.Asp224Glu	missense	Exon 4 of 5	NP_055476.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53B	ENST00000337318.8	TSL:1 MANE Select	c.672C>G	p.Asp224Glu	missense	Exon 4 of 5	ENSP00000338532.3	Q14153-1
	FAM53B	ENST00000280780.6	TSL:1	c.672C>G	p.Asp224Glu	missense	Exon 4 of 5	ENSP00000280780.6	Q14153-2
	ENSG00000258539	ENST00000494792.1	TSL:5	n.*869C>G		non_coding_transcript_exon	Exon 9 of 10	ENSP00000455755.1	H3BQF6

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152266 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.00000816 AC: 2 AN: 245042 AF XY: 0.00000751

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: 0.0000181

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1459858 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726054

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 85966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111116

Other (OTH) AF: 0.00 AC: 0 AN: 60276

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152266 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74396

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68048

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

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000165 AC: 2

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	0.23
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.063
Eigen_PC	Benign	-0.031
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.17
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.045
Sift	Uncertain	0.027	D
Sift4G	Benign	0.10	T
Polyphen		0.61	P
Vest4		0.20
MutPred		0.31		Loss of sheet (P = 0.0315)
MVP		0.52
MPC		0.95
ClinPred		0.33	T
GERP RS		3.3
Varity_R		0.059
gMVP		0.078
Mutation Taster		=87/13	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: rs754765742; hg19: chr10-126370410;