20-10045596-A-T

Position:

• chr20-10045596-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022096.6(ANKEF1):​c.719A>T​(p.Tyr240Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKEF1 NM_022096.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

Genes affected

ANKEF1 (HGNC:15803): (ankyrin repeat and EF-hand domain containing 1) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25995028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKEF1	NM_022096.6	c.719A>T	p.Tyr240Phe	missense_variant	6/11	ENST00000378392.6	NP_071379.3
SNAP25-AS1	NR_040710.1	n.500-18948T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKEF1	ENST00000378392.6	c.719A>T	p.Tyr240Phe	missense_variant	6/11	1	NM_022096.6	ENSP00000367644	P1
SNAP25-AS1	ENST00000421143.6	n.235-18948T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.719A>T (p.Y240F) alteration is located in exon 6 (coding exon 4) of the ANKEF1 gene. This alteration results from a A to T substitution at nucleotide position 719, causing the tyrosine (Y) at amino acid position 240 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.10
Sift	Benign	0.20	T;T
Sift4G	Uncertain	0.059	T;T
Polyphen		0.013	B;B
Vest4		0.52
MutPred		0.47		Gain of ubiquitination at K235 (P = 0.135);Gain of ubiquitination at K235 (P = 0.135);
MVP		0.51
MPC		0.65
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-10026244;