Genetic Variant ANKRD36:p.Cys445Cys (chr2-97158601-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001354587.1(ANKRD36):c.1335T>C(p.Cys445Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000553 in 1,536,038 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00058 ( 5 hom. )

Consequence

ANKRD36
NM_001354587.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.475

Variant links:

Genes affected

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

ANKRD36 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 2-97158601-T-C is Benign according to our data. Variant chr2-97158601-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651161.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.475 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36	NM_001354587.1 link	c.1335T>C	p.Cys445Cys	synonymous_variant	Exon 17 of 76	ENST00000420699.9	NP_001341516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKRD36	ENST00000420699.9 link	c.1335T>C	p.Cys445Cys	synonymous_variant	Exon 17 of 76	5	NM_001354587.1	ENSP00000391950.4	A6QL64-1
ANKRD36	ENST00000461153.7 link	c.1335T>C	p.Cys445Cys	synonymous_variant	Exon 17 of 75	5		ENSP00000419530.3	A6QL64-1
ANKRD36	ENST00000652721.1 link	c.1335T>C	p.Cys445Cys	synonymous_variant	Exon 17 of 76			ENSP00000498611.1	A6QL64-1

Frequencies

GnomAD3 genomes

AF:

0.000323

AC:

AN:

151658

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000615

AC:

AN:

144680

Hom.:

AF XY:

0.000688

AC XY:

AN XY:

77050

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.000489

Gnomad ASJ exome

AF:

0.000712

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000484

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000841

Gnomad OTH exome

AF:

0.00186

GnomAD4 exome

AF:

0.000579

AC:

801

AN:

1384264

Hom.:

Cov.:

AF XY:

0.000609

AC XY:

416

AN XY:

683050

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000505

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000442

Gnomad4 FIN exome

AF:

0.0000286

Gnomad4 NFE exome

AF:

0.000616

Gnomad4 OTH exome

AF:

0.000657

GnomAD4 genome

AF:

0.000323

AC:

AN:

151774

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

AN XY:

74126

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000321

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANKRD36: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

6.5

DANN

Benign

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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