rs1323617086

Variant names:

• chr12-130162987-G-A
• NM_007197.4:c.45G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-130162987-G-A
• chr12-130162987-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_007197.4(FZD10):​c.45G>A​(p.Met15Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000353 in 1,417,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: FZD10 NM_007197.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05

Genes affected

FZD10 (HGNC:4039): (frizzled class receptor 10) This gene is a member of the frizzled gene family. Members of this family encode 7-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. Using array analysis, expression of this intronless gene is significantly up-regulated in two cases of primary colon cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12172145).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FZD10	NM_007197.4	c.45G>A	p.Met15Ile	missense_variant	Exon 1 of 1	ENST00000229030.5	NP_009128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FZD10	ENST00000229030.5	c.45G>A	p.Met15Ile	missense_variant	Exon 1 of 1	6	NM_007197.4	ENSP00000229030.4
FZD10	ENST00000539839	c.-54G>A		5_prime_UTR_variant	Exon 1 of 1			ENSP00000438460.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000353 AC: 5 AN: 1417378 Hom.: 0 Cov.: 32 AF XY: 0.00000285 AC XY: 2 AN XY: 700606

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: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000367

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.16
Sift	Benign	0.34	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.54		Loss of catalytic residue at V11 (P = 0.0373);
MVP		0.16
ClinPred		0.25	T
GERP RS		2.5
Varity_R		0.074
gMVP		0.26

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: chr12-130647532;