chr3-186640669-C-A

Variant names:

• chr3-186640669-C-A
• rs370379105
• NM_014375.3:c.209C>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014375.3(FETUB):​c.209C>A​(p.Ala70Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FETUB NM_014375.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FETUB	NM_014375.3	c.209C>A	p.Ala70Asp	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.209C>A	p.Ala70Asp	missense_variant	Exon 1 of 7	1	NM_014375.3	ENSP00000265029.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249720 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461452 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727072

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T;.;T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.74	.;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.89	D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.7	M;.;M;M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.2	D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.0080	D;T;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.61
MutPred		0.87		Gain of disorder (P = 0.0355);Gain of disorder (P = 0.0355);Gain of disorder (P = 0.0355);Gain of disorder (P = 0.0355);
MVP		0.31
MPC		0.25
ClinPred		0.98	D
GERP RS		-6.3
Varity_R		0.96
gMVP		0.87

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

LitVar

Other links and lift over

dbSNP: rs370379105; hg19: chr3-186358458;