rs139757926

Variant names:

• chr20-10044403-C-A
• rs139757926
• NM_022096.6:c.556C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-10044403-C-A
• chr20-10044403-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022096.6(ANKEF1):​c.556C>A​(p.Arg186Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,656 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. R186C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ANKEF1 NM_022096.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

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.556C>A	p.Arg186Ser	missense	Exon 5 of 11	NP_071379.3
	ANKEF1	NM_198798.3		c.556C>A	p.Arg186Ser	missense	Exon 4 of 10	NP_942093.1	Q9NU02
	ANKEF1	NM_001303472.2		c.-12C>A		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.556C>A	p.Arg186Ser	missense	Exon 5 of 11	ENSP00000367644.1	Q9NU02
	ANKEF1	ENST00000378380.4	TSL:2	c.556C>A	p.Arg186Ser	missense	Exon 4 of 10	ENSP00000367631.3	Q9NU02
	ANKEF1	ENST00000937999.1		c.556C>A	p.Arg186Ser	missense	Exon 4 of 10	ENSP00000608058.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251284 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461656 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111880

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.0083	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.22
Sift	Benign	0.034	D
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.61		Gain of glycosylation at R186 (P = 0.0253)
MVP		0.75
MPC		0.77
ClinPred		0.90	D
GERP RS		5.2
Varity_R		0.38
gMVP		0.75
Mutation Taster		=89/11	polymorphism

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: rs139757926; hg19: chr20-10025051; COSMIC: COSV106064696; COSMIC: COSV106064696;