NM_022096.6:c.320T>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• 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, 0.797

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.320T>C	p.Met107Thr	missense	Exon 3 of 11	NP_071379.3
	ANKEF1	NM_198798.3		c.320T>C	p.Met107Thr	missense	Exon 2 of 10	NP_942093.1	Q9NU02
	ANKEF1	NM_001303472.2		c.-294T>C		5_prime_UTR	Exon 2 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.320T>C	p.Met107Thr	missense	Exon 3 of 11	ENSP00000367644.1	Q9NU02
	ANKEF1	ENST00000378380.4	TSL:2	c.320T>C	p.Met107Thr	missense	Exon 2 of 10	ENSP00000367631.3	Q9NU02
	ANKEF1	ENST00000937999.1		c.320T>C	p.Met107Thr	missense	Exon 2 of 10	ENSP00000608058.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33092

American (AMR) AF: 0.00 AC: 0 AN: 43970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25876

East Asian (EAS) AF: 0.00 AC: 0 AN: 39232

South Asian (SAS) AF: 0.00 AC: 0 AN: 85222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000636 AC: 7 AN: 1099950

Other (OTH) AF: 0.0000168 AC: 1 AN: 59664

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.54		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
Mutation Taster		=70/30	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: rs539927439; hg19: chr20-10019269;