17-4169260-AC-GA

Variant names:

• chr17-4169260-AC-GA
• NM_001330063.2:c.3314_3315delGTinsTC
• ANKFY1 p.Cys1105Phe

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001330063.2(ANKFY1):​c.3314_3315delGTinsTC​(p.Cys1105Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1105S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKFY1 NM_001330063.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

ANKFY1 (HGNC:20763): (ankyrin repeat and FYVE domain containing 1) This gene encodes a cytoplasmic protein that contains a coiled-coil structure and a BTB/POZ domain at its N-terminus, ankyrin repeats in the middle portion, and a FYVE-finger motif at its C-terminus. This protein belongs to a subgroup of double zinc finger proteins which may be involved in vesicle or protein transport. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, Apr 2012]

CYB5D2 (HGNC:28471): (cytochrome b5 domain containing 2) Predicted to enable heme binding activity. Predicted to be involved in nervous system development. Predicted to act upstream of or within positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in endomembrane system and membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330063.2. 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
	ANKFY1	NM_001330063.2	MANE Select	c.3314_3315delGTinsTC	p.Cys1105Phe	missense	N/A	NP_001316992.1	Q9P2R3-1
	ANKFY1	NM_001257999.3		c.3440_3441delGTinsTC	p.Cys1147Phe	missense	N/A	NP_001244928.1	Q9P2R3-4
	ANKFY1	NM_016376.5		c.3317_3318delGTinsTC	p.Cys1106Phe	missense	N/A	NP_057460.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKFY1	ENST00000341657.9	TSL:5 MANE Select	c.3314_3315delGTinsTC	p.Cys1105Phe	missense	N/A	ENSP00000343362.4	Q9P2R3-1
	ANKFY1	ENST00000570535.5	TSL:1	c.3440_3441delGTinsTC	p.Cys1147Phe	missense	N/A	ENSP00000459943.1	Q9P2R3-4
	ANKFY1	ENST00000574367.5	TSL:1	c.3317_3318delGTinsTC	p.Cys1106Phe	missense	N/A	ENSP00000459775.1	Q9P2R3-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.9

Splicing

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

hg19: chr17-4072554;