NM_014375.3:c.401C>T

Variant names:

• chr3-186642535-C-T
• rs1579036306
• NM_014375.3:c.401C>T

Variant summary

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

The NM_014375.3(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 NM_014375.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014375.3. 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
	FETUB	NM_014375.3	MANE Select	c.401C>T	p.Ala134Val	missense	Exon 3 of 7	NP_055190.2	Q9UGM5-1
	FETUB	NM_001375587.2		c.401C>T	p.Ala134Val	missense	Exon 4 of 8	NP_001362516.1	Q9UGM5-1
	FETUB	NM_001308077.4		c.290C>T	p.Ala97Val	missense	Exon 2 of 6	NP_001295006.1	Q9UGM5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FETUB	ENST00000265029.8	TSL:1 MANE Select	c.401C>T	p.Ala134Val	missense	Exon 3 of 7	ENSP00000265029.3	Q9UGM5-1
	FETUB	ENST00000450521.5	TSL:1	c.401C>T	p.Ala134Val	missense	Exon 4 of 8	ENSP00000404288.1	Q9UGM5-1
	FETUB	ENST00000382136.3	TSL:1	c.290C>T	p.Ala97Val	missense	Exon 2 of 6	ENSP00000371571.3	Q9UGM5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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	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
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.9
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.052	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.46		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
Mutation Taster		=41/59	disease causing

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

Other links and lift over

dbSNP: rs1579036306; hg19: chr3-186360324;