Genetic Variant NM_001354587.1:c.3878-4_3878-3dupTT (chr2-97224796-A-ATT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_001354587.1(ANKRD36):c.3878-4_3878-3dupTT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000017 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANKRD36
NM_001354587.1 splice_acceptor, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0630

Publications

0 publications found

Variant links:

Genes affected

ANKRD36 (HGNC:24079): (ankyrin repeat domain 36)

ANKRD36 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.012874044 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.1, offset of 0 (no position change), new splice context is: aatatataatttttttttAGcag. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354587.1. 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
	ANKRD36	NM_001354587.1	MANE Select	c.3878-4_3878-3dupTT		splice_acceptor intron	N/A	NP_001341516.1	A6QL64-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKRD36	ENST00000420699.9	TSL:5 MANE Select	c.3878-10_3878-9insTT	intron	N/A	ENSP00000391950.4	A6QL64-1
ANKRD36	ENST00000461153.7	TSL:5	c.3878-10_3878-9insTT	intron	N/A	ENSP00000419530.3	A6QL64-1
ANKRD36	ENST00000652721.1		c.3878-10_3878-9insTT	intron	N/A	ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes

AF:

0.0000175

AC:

AN:

114340

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000333

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000175

AC:

AN:

1140714

Hom.:

Cov.:

AF XY:

0.00000178

AC XY:

AN XY:

561274

show subpopulations

African (AFR)

AF:

0.0000617

AC:

AN:

16202

American (AMR)

AF:

0.00

AC:

AN:

22568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20268

East Asian (EAS)

AF:

0.00

AC:

AN:

19120

South Asian (SAS)

AF:

0.00

AC:

AN:

38132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3074

European-Non Finnish (NFE)

AF:

0.00000108

AC:

AN:

927924

Other (OTH)

AF:

0.00

AC:

AN:

45492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000175

AC:

AN:

114340

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

55450

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

24324

American (AMR)

AF:

0.00

AC:

AN:

10272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2606

East Asian (EAS)

AF:

0.00

AC:

AN:

2578

South Asian (SAS)

AF:

0.00

AC:

AN:

2064

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.0000333

AC:

AN:

60120

Other (OTH)

AF:

0.00

AC:

AN:

1566

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.063

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over