chr17-4172671-T-G

Variant names:

• chr17-4172671-T-G
• rs200094920
• NM_001330063.2:c.3024A>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001330063.2(ANKFY1):​c.3024A>C​(p.Ser1008Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (0 hom.)
• Consequence: ANKFY1 NM_001330063.2 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.14
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-4172671-T-G is Benign according to our data. Variant chr17-4172671-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3035702.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.14 with no splicing effect.

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.3024A>C	p.Ser1008Ser	synonymous	Exon 22 of 25	NP_001316992.1	Q9P2R3-1
	ANKFY1	NM_001257999.3		c.3150A>C	p.Ser1050Ser	synonymous	Exon 22 of 25	NP_001244928.1	Q9P2R3-4
	ANKFY1	NM_016376.5		c.3027A>C	p.Ser1009Ser	synonymous	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.3024A>C	p.Ser1008Ser	synonymous	Exon 22 of 25	ENSP00000343362.4	Q9P2R3-1
	ANKFY1	ENST00000570535.5	TSL:1	c.3150A>C	p.Ser1050Ser	synonymous	Exon 22 of 25	ENSP00000459943.1	Q9P2R3-4
	ANKFY1	ENST00000574367.5	TSL:1	c.3027A>C	p.Ser1009Ser	synonymous	Exon 22 of 25	ENSP00000459775.1	Q9P2R3-2

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152228 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

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: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000165 AC: 41 AN: 248930 AF XY: 0.000178

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000318

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000389 AC: 568 AN: 1461628 Hom.: 0 Cov.: 30 AF XY: 0.000337 AC XY: 245 AN XY: 727120

African (AFR) AF: 0.000119 AC: 4 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000498 AC: 554 AN: 1111910

Other (OTH) AF: 0.000132 AC: 8 AN: 60386

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74382

African (AFR) AF: 0.0000724 AC: 3 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

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

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000212 Hom.: 0

Bravo AF: 0.000166

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ANKFY1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-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

Other links and lift over

dbSNP: rs200094920; hg19: chr17-4075966;