NM_001330063.2:c.3314G>T

Variant names:

• chr17-4169261-C-A
• rs531938826
• NM_001330063.2:c.3314G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001330063.2(ANKFY1):​c.3314G>T​(p.Cys1105Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.869

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.3314G>T	p.Cys1105Phe	missense	Exon 24 of 25	NP_001316992.1	Q9P2R3-1
	ANKFY1	NM_001257999.3		c.3440G>T	p.Cys1147Phe	missense	Exon 24 of 25	NP_001244928.1	Q9P2R3-4
	ANKFY1	NM_016376.5		c.3317G>T	p.Cys1106Phe	missense	Exon 24 of 25	NP_057460.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKFY1	ENST00000341657.9	TSL:5 MANE Select	c.3314G>T	p.Cys1105Phe	missense	Exon 24 of 25	ENSP00000343362.4	Q9P2R3-1
	ANKFY1	ENST00000570535.5	TSL:1	c.3440G>T	p.Cys1147Phe	missense	Exon 24 of 25	ENSP00000459943.1	Q9P2R3-4
	ANKFY1	ENST00000574367.5	TSL:1	c.3317G>T	p.Cys1106Phe	missense	Exon 24 of 25	ENSP00000459775.1	Q9P2R3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.80	T
REVEL	Uncertain	0.42
Sift4G	Uncertain	0.025	D
Polyphen		0.99	D
Vest4		0.87
MutPred		0.54		Loss of loop (P = 0.0128)
MVP		0.95
MPC		1.4
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.67
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs531938826; hg19: chr17-4072555;