chr3-186642553-G-C

Variant names:

• chr3-186642553-G-C
• NM_014375.3:c.419G>C

Variant summary

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

The NM_014375.3(FETUB):​c.419G>C​(p.Arg140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,430,558 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FETUB NM_014375.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50

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.419G>C	p.Arg140Pro	missense_variant	Exon 3 of 7	ENST00000265029.8	NP_055190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FETUB	ENST00000265029.8	c.419G>C	p.Arg140Pro	missense_variant	Exon 3 of 7	1	NM_014375.3	ENSP00000265029.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1430558 Hom.: 0 Cov.: 24 AF XY: 0.00000140 AC XY: 1 AN XY: 713320

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T;T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.80	.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.022	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.61
MutPred		0.58		Loss of MoRF binding (P = 0.0455);Loss of MoRF binding (P = 0.0455);.;
MVP		0.44
MPC		0.25
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.83
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.22		Position offset: 5

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: chr3-186360342;