NM_001330063.2:c.3124G>A

Variant names:

• chr17-4172571-C-T
• rs895193667
• NM_001330063.2:c.3124G>A

Variant summary

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

The NM_001330063.2(ANKFY1):​c.3124G>A​(p.Ala1042Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANKFY1 NM_001330063.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08739415).

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.3124G>A	p.Ala1042Thr	missense	Exon 22 of 25	NP_001316992.1	Q9P2R3-1
	ANKFY1	NM_001257999.3		c.3250G>A	p.Ala1084Thr	missense	Exon 22 of 25	NP_001244928.1	Q9P2R3-4
	ANKFY1	NM_016376.5		c.3127G>A	p.Ala1043Thr	missense	Exon 22 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.3124G>A	p.Ala1042Thr	missense	Exon 22 of 25	ENSP00000343362.4	Q9P2R3-1
	ANKFY1	ENST00000570535.5	TSL:1	c.3250G>A	p.Ala1084Thr	missense	Exon 22 of 25	ENSP00000459943.1	Q9P2R3-4
	ANKFY1	ENST00000574367.5	TSL:1	c.3127G>A	p.Ala1043Thr	missense	Exon 22 of 25	ENSP00000459775.1	Q9P2R3-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461550 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727080

African (AFR) AF: 0.0000299 AC: 1 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111822

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74374

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.073
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.9
DANN	Uncertain	0.97
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.5
PrimateAI	Benign	0.39	T
REVEL	Benign	0.031
Sift4G	Benign	0.26	T
Polyphen		0.55	P
Vest4		0.16
MutPred		0.29		Gain of phosphorylation at A1042 (P = 0.0463)
MVP		0.59
MPC		0.42
ClinPred		0.10	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.016
gMVP		0.23
Mutation Taster		=87/13	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: rs895193667; hg19: chr17-4075866;