rs1007141421

Variant names:

• chr12-65051390-C-G
• NM_007191.5:c.1099G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-65051390-C-G
• chr12-65051390-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007191.5(WIF1):​c.1099G>C​(p.Glu367Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: WIF1 NM_007191.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06

Genes affected

WIF1 (HGNC:18081): (WNT inhibitory factor 1) The protein encoded by this gene functions to inhibit WNT proteins, which are extracellular signaling molecules that play a role in embryonic development. This protein contains a WNT inhibitory factor (WIF) domain and five epidermal growth factor (EGF)-like domains, and is thought to be involved in mesoderm segmentation. This gene functions as a tumor suppressor gene, and has been found to be epigenetically silenced in various cancers. [provided by RefSeq, Jun 2010]

ENSG00000198671 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29393217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIF1	NM_007191.5	c.1099G>C	p.Glu367Gln	missense_variant	Exon 10 of 10	ENST00000286574.9	NP_009122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIF1	ENST00000286574.9	c.1099G>C	p.Glu367Gln	missense_variant	Exon 10 of 10	1	NM_007191.5	ENSP00000286574.4
WIF1	ENST00000543094.1	c.346G>C	p.Glu116Gln	missense_variant	Exon 5 of 5	5		ENSP00000439024.1
ENSG00000198671	ENST00000360528.3	n.1036-2712C>G		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461620 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727124

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T
Eigen	Benign	0.065
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.27
Sift	Benign	0.031	D;T
Sift4G	Uncertain	0.030	D;T
Polyphen		0.32	B;.
Vest4		0.19
MutPred		0.29		Gain of catalytic residue at P372 (P = 9e-04);.;
MVP		0.89
MPC		0.18
ClinPred		0.44	T
GERP RS		5.4
Varity_R		0.13
gMVP		0.48

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: chr12-65445170;