Genetic Variant ANKMY1:p.Cys1009Cys (chr2-240480956-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001282771.3(ANKMY1):c.3027C>T(p.Cys1009Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,611,586 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0051 ( 39 hom. )

Consequence

ANKMY1
NM_001282771.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.370

Publications

3 publications found

Variant links:

Genes affected

ANKMY1 (HGNC:20987): (ankyrin repeat and MYND domain containing 1) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ANKMY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-240480956-G-A is Benign according to our data. Variant chr2-240480956-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2652090.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.37 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282771.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKMY1	NM_001282771.3	MANE Select	c.3027C>T	p.Cys1009Cys	synonymous	Exon 17 of 18	NP_001269700.1	J3KQ21
ANKMY1	NM_001354023.3		c.3027C>T	p.Cys1009Cys	synonymous	Exon 18 of 19	NP_001340952.1	J3KQ21
ANKMY1	NM_001393462.1		c.2943C>T	p.Cys981Cys	synonymous	Exon 17 of 18	NP_001380391.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKMY1	ENST00000401804.6	TSL:1 MANE Select	c.3027C>T	p.Cys1009Cys	synonymous	Exon 17 of 18	ENSP00000385887.1	J3KQ21
ANKMY1	ENST00000272972.7	TSL:1	c.2760C>T	p.Cys920Cys	synonymous	Exon 16 of 17	ENSP00000272972.3	Q9P2S6-1
ANKMY1	ENST00000403283.6	TSL:1	c.2466C>T	p.Cys822Cys	synonymous	Exon 14 of 15	ENSP00000383968.1	J3KPY5

Frequencies

GnomAD3 genomes

AF:

0.00426

AC:

649

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00546

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00623

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00510

AC:

1281

AN:

251074

AF XY:

0.00516

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00125

Gnomad ASJ exome

AF:

0.0229

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00584

Gnomad NFE exome

AF:

0.00657

Gnomad OTH exome

AF:

0.00442

GnomAD4 exome

AF:

0.00507

AC:

7397

AN:

1459282

Hom.:

Cov.:

AF XY:

0.00515

AC XY:

3737

AN XY:

725428

show subpopulations

African (AFR)

AF:

0.000688

AC:

AN:

33444

American (AMR)

AF:

0.00148

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.0240

AC:

626

AN:

26108

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39580

South Asian (SAS)

AF:

0.00426

AC:

367

AN:

86186

European-Finnish (FIN)

AF:

0.00595

AC:

317

AN:

53310

Middle Eastern (MID)

AF:

0.00576

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00502

AC:

5577

AN:

1110012

Other (OTH)

AF:

0.00641

AC:

386

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

427

854

1280

1707

2134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00426

AC:

649

AN:

152304

Hom.:

Cov.:

AF XY:

0.00438

AC XY:

326

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41566

American (AMR)

AF:

0.00144

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0236

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00290

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00546

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00623

AC:

424

AN:

68032

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

103

138

172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00609

Hom.:

Bravo

AF:

0.00356

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00573

EpiControl

AF:

0.00623

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.6

(source)

DANN

Benign

0.77

PhyloP100

-0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over