17-56350816-A-T

Variant names:

• chr17-56350816-A-T
• rs1283573053
• NM_001370326.1:c.239A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370326.1(ANKFN1):​c.239A>T​(p.Gln80Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q80R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANKFN1 NM_001370326.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.79
• Publications: 0 publications found

Genes affected

ANKFN1 (HGNC:26766): (ankyrin repeat and fibronectin type III domain containing 1) Predicted to be involved in establishment of mitotic spindle orientation and regulation of establishment of bipolar cell polarity. Predicted to act upstream of or within behavioral fear response; equilibrioception; and locomotor rhythm. Predicted to be active in spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32878155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKFN1	NM_001370326.1	c.239A>T	p.Gln80Leu	missense_variant	Exon 5 of 21	ENST00000682825.1	NP_001357255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKFN1	ENST00000682825.1	c.239A>T	p.Gln80Leu	missense_variant	Exon 5 of 21		NM_001370326.1	ENSP00000507365.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461598 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727104

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111846

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T;T;T;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	.;L;.;.
PhyloP100		5.8
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.0	.;D;.;.
REVEL	Benign	0.13
Sift	Benign	0.049	.;D;.;.
Sift4G	Benign	0.067	.;T;T;T
Polyphen		0.90	.;P;.;.
Vest4		0.69, 0.70
MutPred		0.19		.;Gain of catalytic residue at Q83 (P = 0.0156);Gain of catalytic residue at Q83 (P = 0.0156);.;
MVP		0.71
MPC		0.56
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.29
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1283573053; hg19: chr17-54428177;