Genetic Variant NM_001330063.2:c.3378-97C>T (chr17-4168008-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001330063.2(ANKFY1):c.3378-97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANKFY1
NM_001330063.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

Variant links:

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]

ANKFY1 links:

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]

CYB5D2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKFY1	NM_001330063.2 link	c.3378-97C>T		intron_variant	Intron 24 of 24	ENST00000341657.9	NP_001316992.1	Q9P2R3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKFY1	ENST00000341657.9 link	c.3378-97C>T		intron_variant	Intron 24 of 24	5	NM_001330063.2	ENSP00000343362.4		Q9P2R3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1239548

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

610740

African (AFR)

AF:

0.00

AC:

AN:

27842

American (AMR)

AF:

0.00

AC:

AN:

28028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19048

East Asian (EAS)

AF:

0.00

AC:

AN:

36764

South Asian (SAS)

AF:

0.00

AC:

AN:

62406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4500

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

967572

Other (OTH)

AF:

0.00

AC:

AN:

51386

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1321

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.1

(source)

DANN

Benign

0.77

PhyloP100

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over