Genetic Variant ANKRD36C:c.1633+1G>A (chr2-95938828-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_001393982.1(ANKRD36C):c.1633+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 131,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 132)

Exomes 𝑓: 0.000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANKRD36C
NM_001393982.1 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 1.79

Variant links:

Genes affected

ANKRD36C (HGNC:32946): (ankyrin repeat domain 36C)

ANKRD36C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.011477987 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.5, offset of -27, new splice context is: gaaGTatgg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36C	NM_001393982.1 link	c.1633+1G>A		splice_donor_variant, intron_variant	Intron 22 of 87	ENST00000295246.7	NP_001380911.1
ANKRD36C	NM_001310154.3 link	c.1633+1G>A		splice_donor_variant, intron_variant	Intron 22 of 88		NP_001297083.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKRD36C	ENST00000295246.7 link	c.1633+1G>A	splice_donor_variant, intron_variant	Intron 22 of 87	5	NM_001393982.1	ENSP00000295246.7	A0A8J8YUB5
ANKRD36C	ENST00000456556.5 link	c.1633+1G>A	splice_donor_variant, intron_variant	Intron 22 of 66	5		ENSP00000403302.1	Q5JPF3-1
ANKRD36C	ENST00000528268.5 link	n.1560+159G>A	intron_variant	Intron 21 of 26	2		ENSP00000431824.1	E9PJI0
ANKRD36C	ENST00000534304.5 link	n.144+159G>A	intron_variant	Intron 4 of 42	5		ENSP00000433685.1	H0YDI7

Frequencies

GnomAD3 genomes

AF:

0.0000229

AC:

AN:

131142

Hom.:

Cov.:

132

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:

0.000120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000336

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000456

AC:

AN:

129388

Hom.:

AF XY:

0.000976

AC XY:

AN XY:

60426

show subpopulations

Gnomad AFR exome

AF:

0.000266

Gnomad AMR exome

AF:

0.000270

Gnomad ASJ exome

AF:

0.000133

Gnomad EAS exome

AF:

0.000105

Gnomad SAS exome

AF:

0.000693

Gnomad FIN exome

AF:

0.000315

Gnomad NFE exome

AF:

0.000634

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000287

AC:

AN:

1323614

Hom.:

Cov.:

121

AF XY:

0.0000611

AC XY:

AN XY:

621894

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000121

Gnomad4 ASJ exome

AF:

0.0000850

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000179

Gnomad4 FIN exome

AF:

0.000119

Gnomad4 NFE exome

AF:

0.0000106

Gnomad4 OTH exome

AF:

0.0000541

GnomAD4 genome

AF:

0.0000229

AC:

AN:

131228

Hom.:

Cov.:

132

AF XY:

0.0000562

AC XY:

AN XY:

53360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000120

Gnomad4 NFE

AF:

0.0000336

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00699

Hom.:

ExAC

AF:

0.0136

AC:

354

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

CIC-rearranged sarcoma

Other:1

Children's Cancer Therapy Development Institute

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.76

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.20

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.77

SpliceAI score (max)

0.53

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.53

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over