chr12-65051449-T-C

Variant names:

• chr12-65051449-T-C
• rs771969291
• NM_007191.5:c.1040A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007191.5(WIF1):​c.1040A>G​(p.His347Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,611,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: WIF1 NM_007191.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15746146).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007191.5. 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
	WIF1	NM_007191.5	MANE Select	c.1040A>G	p.His347Arg	missense	Exon 10 of 10	NP_009122.2	Q9Y5W5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIF1	ENST00000286574.9	TSL:1 MANE Select	c.1040A>G	p.His347Arg	missense	Exon 10 of 10	ENSP00000286574.4	Q9Y5W5
	WIF1	ENST00000954483.1		c.1010A>G	p.His337Arg	missense	Exon 10 of 10	ENSP00000624542.1
	WIF1	ENST00000954485.1		c.1010A>G	p.His337Arg	missense	Exon 10 of 10	ENSP00000624544.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152252 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000366 AC: 9 AN: 245604 AF XY: 0.0000526

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000722

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000336 AC: 49 AN: 1459270 Hom.: 0 Cov.: 30 AF XY: 0.0000399 AC XY: 29 AN XY: 725942

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39532

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1111060

Other (OTH) AF: 0.0000497 AC: 3 AN: 60304

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152252 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74376

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68052

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000160 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000494 AC: 6

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	Benign	0.058
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.015
Sift	Benign	0.23	T
Sift4G	Benign	0.098	T
Polyphen		0.021	B
Vest4		0.16
MVP		0.63
MPC		0.18
ClinPred		0.041	T
GERP RS		3.0
Varity_R		0.053
gMVP		0.34
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs771969291; hg19: chr12-65445229;