20-10044410-C-T

Variant names:

• chr20-10044410-C-T
• rs757633997
• NM_022096.6:c.563C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022096.6(ANKEF1):​c.563C>T​(p.Ala188Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A188D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKEF1 NM_022096.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022096.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKEF1	NM_022096.6	MANE Select	c.563C>T	p.Ala188Val	missense	Exon 5 of 11	NP_071379.3
	ANKEF1	NM_198798.3		c.563C>T	p.Ala188Val	missense	Exon 4 of 10	NP_942093.1	Q9NU02
	ANKEF1	NM_001303472.2		c.-5C>T		5_prime_UTR	Exon 5 of 11	NP_001290401.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKEF1	ENST00000378392.6	TSL:1 MANE Select	c.563C>T	p.Ala188Val	missense	Exon 5 of 11	ENSP00000367644.1	Q9NU02
	ANKEF1	ENST00000378380.4	TSL:2	c.563C>T	p.Ala188Val	missense	Exon 4 of 10	ENSP00000367631.3	Q9NU02
	ANKEF1	ENST00000937999.1		c.563C>T	p.Ala188Val	missense	Exon 4 of 10	ENSP00000608058.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000193 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.080
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.011	D
Polyphen		0.65	P
Vest4		0.39
MutPred		0.80		Loss of disorder (P = 0.0731)
MVP		0.81
MPC		0.25
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.28
gMVP		0.70
Mutation Taster		=48/52	disease causing

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

Other links and lift over

dbSNP: rs757633997; hg19: chr20-10025058;