rs771072670

Variant names:

• chr20-10038569-G-A
• rs771072670
• NM_022096.6:c.268G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-10038569-G-A
• chr20-10038569-G-C

Variant summary

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

The NM_022096.6(ANKEF1):​c.268G>A​(p.Glu90Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,882 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E90Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: ANKEF1 NM_022096.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.96

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, 0.792

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKEF1	NM_022096.6	c.268G>A	p.Glu90Lys	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.268G>A	p.Glu90Lys	missense_variant	Exon 3 of 11	1	NM_022096.6	ENSP00000367644.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461882 Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 17 AN XY: 727238

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: 0.0000351

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.045	T;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.077	T;T
Polyphen		1.0	D;D
Vest4		0.74
MutPred		0.43		Gain of ubiquitination at E90 (P = 0.0388);Gain of ubiquitination at E90 (P = 0.0388);
MVP		0.83
MPC		0.75
ClinPred		0.84	D
GERP RS		5.9
Varity_R		0.52
gMVP		0.74

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: rs771072670; hg19: chr20-10019217;