NM_001330063.2:c.3140-106T>G

Variant names:

• chr17-4170967-A-C
• rs897030
• NM_001330063.2:c.3140-106T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001330063.2(ANKFY1):​c.3140-106T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,522,498 control chromosomes in the GnomAD database, including 759,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75482 hom., cov: 33)
  • Exomes 𝑓: 1.0 (684423 hom.)
• Consequence: ANKFY1 NM_001330063.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.631
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-4170967-A-C is Benign according to our data. Variant chr17-4170967-A-C is described in ClinVar as Benign. ClinVar VariationId is 1288285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

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.3140-106T>G		intron	N/A	NP_001316992.1	Q9P2R3-1
	ANKFY1	NM_001257999.3		c.3266-106T>G		intron	N/A	NP_001244928.1	Q9P2R3-4
	ANKFY1	NM_016376.5		c.3143-106T>G		intron	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.3140-106T>G		intron	N/A	ENSP00000343362.4	Q9P2R3-1
	ANKFY1	ENST00000570535.5	TSL:1	c.3266-106T>G		intron	N/A	ENSP00000459943.1	Q9P2R3-4
	ANKFY1	ENST00000574367.5	TSL:1	c.3143-106T>G		intron	N/A	ENSP00000459775.1	Q9P2R3-2

Frequencies

GnomAD3 genomes AF: 0.995 AC: 151525 AN: 152224 Hom.: 75422 Cov.: 33

Gnomad AFR AF: 0.984

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.998

GnomAD4 exome AF: 1.00 AC: 1369497 AN: 1370156 Hom.: 684423 AF XY: 1.00 AC XY: 681922 AN XY: 682200

African (AFR) AF: 0.984 AC: 30974 AN: 31472

American (AMR) AF: 1.00 AC: 40249 AN: 40268

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 24701 AN: 24702

East Asian (EAS) AF: 1.00 AC: 38120 AN: 38120

South Asian (SAS) AF: 1.00 AC: 81267 AN: 81270

European-Finnish (FIN) AF: 1.00 AC: 46382 AN: 46382

Middle Eastern (MID) AF: 0.999 AC: 4270 AN: 4276

European-Non Finnish (NFE) AF: 1.00 AC: 1046599 AN: 1046676

Other (OTH) AF: 0.999 AC: 56935 AN: 56990

GnomAD4 genome AF: 0.995 AC: 151644 AN: 152342 Hom.: 75482 Cov.: 33 AF XY: 0.995 AC XY: 74147 AN XY: 74484

African (AFR) AF: 0.984 AC: 40922 AN: 41578

American (AMR) AF: 0.998 AC: 15272 AN: 15302

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 1.00 AC: 4828 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68032 AN: 68040

Other (OTH) AF: 0.998 AC: 2110 AN: 2114

Alfa AF: 0.997 Hom.: 21821

Bravo AF: 0.995

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

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: rs897030; hg19: chr17-4074261;