20-10038317-A-G

Variant names:

• chr20-10038317-A-G
• NM_022096.6:c.16A>G

Variant summary

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

The NM_001303472.2(ANKEF1):​c.-598A>G variant causes a 5 prime UTR premature start codon gain 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)
• Consequence: ANKEF1 NM_001303472.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

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=0.09856948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKEF1	NM_022096.6	c.16A>G	p.Lys6Glu	missense_variant	Exon 3 of 11	ENST00000378392.6	NP_071379.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKEF1	ENST00000378392.6	c.16A>G	p.Lys6Glu	missense_variant	Exon 3 of 11	1	NM_022096.6	ENSP00000367644.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16A>G (p.K6E) alteration is located in exon 3 (coding exon 1) of the ANKEF1 gene. This alteration results from a A to G substitution at nucleotide position 16, causing the lysine (K) at amino acid position 6 to be replaced by a glutamic acid (E). 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	0.096
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.57	.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.050
Sift	Benign	0.53	T;T
Sift4G	Benign	0.74	T;T
Polyphen		0.0080	B;B
Vest4		0.13
MutPred		0.36		Loss of ubiquitination at K6 (P = 0.0167);Loss of ubiquitination at K6 (P = 0.0167);
MVP		0.72
MPC		0.28
ClinPred		0.24	T
GERP RS		4.8
Varity_R		0.14
gMVP		0.73

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: chr20-10018965;