3-186640593-G-A

Variant names:

• chr3-186640593-G-A
• NM_014375.3:c.133G>A

Variant summary

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

The NM_014375.3(FETUB):​c.133G>A​(p.Ala45Thr) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: FETUB NM_014375.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.336

Genes affected

FETUB (HGNC:3658): (fetuin B) The protein encoded by this gene is a member of the fetuin family, part of the cystatin superfamily of cysteine protease inhibitors. Fetuins have been implicated in several diverse functions, including osteogenesis and bone resorption, regulation of the insulin and hepatocyte growth factor receptors, and response to systemic inflammation. This protein may be secreted by cells. [provided by RefSeq, Jul 2008]

HRG-AS1 (HGNC:55915): (HRG and FETUB antisense RNA 1)

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
FETUB	NM_014375.3	c.133G>A	p.Ala45Thr	missense_variant	Exon 1 of 7	ENST00000265029.8	NP_055190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FETUB	ENST00000265029.8	c.133G>A	p.Ala45Thr	missense_variant	Exon 1 of 7	1	NM_014375.3	ENSP00000265029.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.133G>A (p.A45T) alteration is located in exon 1 (coding exon 1) of the FETUB gene. This alteration results from a G to A substitution at nucleotide position 133, causing the alanine (A) at amino acid position 45 to be replaced by a threonine (T). 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	Benign	0.23
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T;.;T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.68	.;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.2	M;.;M;M
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.036	D;T;D;D
Sift4G	Uncertain	0.056	T;D;T;D
Polyphen		0.57	P;P;P;.
Vest4		0.34
MutPred		0.80		Gain of MoRF binding (P = 0.3398);Gain of MoRF binding (P = 0.3398);Gain of MoRF binding (P = 0.3398);Gain of MoRF binding (P = 0.3398);
MVP		0.35
MPC		0.12
ClinPred		0.79	D
GERP RS		-0.043
Varity_R		0.46
gMVP		0.73

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: chr3-186358382;