3-186642535-C-T

Position:

• chr3-186642535-C-T

Variant summary

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

The ENST00000265029.8(FETUB):​c.401C>T​(p.Ala134Val) variant causes a missense change. 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 ENST00000265029.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93

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/exons	MANE	Protein	UniProt
FETUB	NM_014375.3	c.401C>T	p.Ala134Val	missense_variant	3/7	ENST00000265029.8	NP_055190.2
HRG-AS1	XR_924801.3	n.574-407G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FETUB	ENST00000265029.8	c.401C>T	p.Ala134Val	missense_variant	3/7	1	NM_014375.3	ENSP00000265029	P1
HRG-AS1	ENST00000630178.2	n.239-62569G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.401C>T (p.A134V) alteration is located in exon 3 (coding exon 3) of the FETUB gene. This alteration results from a C to T substitution at nucleotide position 401, causing the alanine (A) at amino acid position 134 to be replaced by a valine (V). 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	Uncertain	0.36
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.068	T;T;.
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M;M;.
MutationTaster	Benign	0.94	D;D;D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.012	D;D;D
Sift4G	Uncertain	0.052	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.53
MutPred		0.46		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;
MVP		0.39
MPC		0.19
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.53
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1579036306; hg19: chr3-186360324;