NM_001330063.2:c.3378-40G>A

Variant names:

• chr17-4167951-C-T
• rs16953763
• NM_001330063.2:c.3378-40G>A

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.3378-40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 1,593,132 control chromosomes in the GnomAD database, including 2,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (145 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2432 hom.)
• Consequence: ANKFY1 NM_001330063.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.588
• 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=-0.88).
• BP6: Variant 17-4167951-C-T is Benign according to our data. Variant chr17-4167951-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0533 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.3378-40G>A		intron	N/A	NP_001316992.1	Q9P2R3-1
	ANKFY1	NM_001257999.3		c.3504-40G>A		intron	N/A	NP_001244928.1	Q9P2R3-4
	ANKFY1	NM_016376.5		c.3381-40G>A		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.3378-40G>A		intron	N/A	ENSP00000343362.4	Q9P2R3-1
	ANKFY1	ENST00000570535.5	TSL:1	c.3504-40G>A		intron	N/A	ENSP00000459943.1	Q9P2R3-4
	ANKFY1	ENST00000574367.5	TSL:1	c.3381-40G>A		intron	N/A	ENSP00000459775.1	Q9P2R3-2

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5854 AN: 152168 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0284

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0382

GnomAD2 exomes AF: 0.0423 AC: 10009 AN: 236762 AF XY: 0.0441

Gnomad AFR exome AF: 0.00999

Gnomad AMR exome AF: 0.0211

Gnomad ASJ exome AF: 0.0139

Gnomad EAS exome AF: 0.000171

Gnomad FIN exome AF: 0.0802

Gnomad NFE exome AF: 0.0550

Gnomad OTH exome AF: 0.0463

GnomAD4 exome AF: 0.0544 AC: 78334 AN: 1440846 Hom.: 2432 Cov.: 30 AF XY: 0.0541 AC XY: 38681 AN XY: 715222

African (AFR) AF: 0.00789 AC: 259 AN: 32842

American (AMR) AF: 0.0222 AC: 954 AN: 42976

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 419 AN: 25254

East Asian (EAS) AF: 0.000102 AC: 4 AN: 39360

South Asian (SAS) AF: 0.0436 AC: 3673 AN: 84214

European-Finnish (FIN) AF: 0.0788 AC: 4110 AN: 52178

Middle Eastern (MID) AF: 0.0464 AC: 262 AN: 5642

European-Non Finnish (NFE) AF: 0.0598 AC: 65767 AN: 1099062

Other (OTH) AF: 0.0487 AC: 2886 AN: 59318

GnomAD4 genome AF: 0.0384 AC: 5850 AN: 152286 Hom.: 145 Cov.: 32 AF XY: 0.0391 AC XY: 2912 AN XY: 74444

African (AFR) AF: 0.0107 AC: 446 AN: 41556

American (AMR) AF: 0.0284 AC: 434 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0350 AC: 169 AN: 4826

European-Finnish (FIN) AF: 0.0856 AC: 907 AN: 10592

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0548 AC: 3726 AN: 68028

Other (OTH) AF: 0.0378 AC: 80 AN: 2114

Alfa AF: 0.0435 Hom.: 32

Bravo AF: 0.0330

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	0.22
DANN	Benign	0.66
PhyloP100		-0.59
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: rs16953763; hg19: chr17-4071245;