20-10038621-T-C

Variant names:

• chr20-10038621-T-C
• rs539927439
• NM_022096.6:c.320T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022096.6(ANKEF1):​c.320T>C​(p.Met107Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000553 in 1,445,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000055 (0 hom.)
• Consequence: ANKEF1 NM_022096.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.39

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKEF1	NM_022096.6	c.320T>C	p.Met107Thr	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.320T>C	p.Met107Thr	missense_variant	Exon 3 of 11	1	NM_022096.6	ENSP00000367644.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000553 AC: 8 AN: 1445976 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 715824

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000636

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.320T>C (p.M107T) alteration is located in exon 3 (coding exon 1) of the ANKEF1 gene. This alteration results from a T to C substitution at nucleotide position 320, causing the methionine (M) at amino acid position 107 to be replaced by a threonine (T). 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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.067	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		1.0	D;D
Vest4		0.88
MutPred		0.54		Gain of ubiquitination at K102 (P = 0.0685);Gain of ubiquitination at K102 (P = 0.0685);
MVP		0.76
MPC		0.78
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.50
gMVP		0.67

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

LitVar

Other links and lift over

dbSNP: rs539927439; hg19: chr20-10019269;