8-103300204-A-T

Variant names:

• chr8-103300204-A-T
• rs827528
• NM_003506.4:c.97A>T

Variant summary

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

The NM_001317796.2(FZD6):​c.-49A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 31)
• Consequence: FZD6 NM_001317796.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 37 publications found

Genes affected

FZD6 (HGNC:4044): (frizzled class receptor 6) This gene represents a member of the 'frizzled' gene family, which encode 7-transmembrane domain proteins that are receptors for Wnt signaling proteins. The protein encoded by this family member contains a signal peptide, a cysteine-rich domain in the N-terminal extracellular region, and seven transmembrane domains, but unlike other family members, this protein does not contain a C-terminal PDZ domain-binding motif. This protein functions as a negative regulator of the canonical Wnt/beta-catenin signaling cascade, thereby inhibiting the processes that trigger oncogenic transformation, cell proliferation, and inhibition of apoptosis. Alternative splicing results in multiple transcript variants, some of which do not encode a protein with a predicted signal peptide.[provided by RefSeq, Aug 2011]

BAALC-AS1 (HGNC:50461): (BAALC antisense RNA 1)

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=0.10744271).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317796.2. 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
	FZD6	NM_003506.4	MANE Select	c.97A>T	p.Met33Leu	missense	Exon 2 of 7	NP_003497.2
	FZD6	NM_001317796.2		c.-49A>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001304725.1
	FZD6	NM_001164615.2		c.97A>T	p.Met33Leu	missense	Exon 2 of 7	NP_001158087.1	O60353-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZD6	ENST00000358755.5	TSL:1 MANE Select	c.97A>T	p.Met33Leu	missense	Exon 2 of 7	ENSP00000351605.4	O60353-1
	FZD6	ENST00000522566.5	TSL:1	c.97A>T	p.Met33Leu	missense	Exon 2 of 7	ENSP00000429055.1	O60353-1
	FZD6	ENST00000522484.5	TSL:1	n.97A>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000428301.1	G5EA13

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
PhyloP100		0.029
Varity_R		0.083
gMVP		0.50
Mutation Taster		=168/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs827528; hg19: chr8-104312432;