Genetic Variant ANKRD36C:p.Asp2046Asn (chr2-95853744-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001393982.1(ANKRD36C):c.6136G>A(p.Asp2046Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00758 in 1,594,738 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0079 ( 75 hom. )

Consequence

ANKRD36C
NM_001393982.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007240534).

BP6

Variant 2-95853744-C-T is Benign according to our data. Variant chr2-95853744-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651123.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD36C	NM_001393982.1 link	c.6136G>A	p.Asp2046Asn	missense_variant	Exon 84 of 88	ENST00000295246.7	NP_001380911.1
ANKRD36C	NM_001310154.3 link	c.6211G>A	p.Asp2071Asn	missense_variant	Exon 85 of 89		NP_001297083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKRD36C	ENST00000295246.7 link	c.6136G>A	p.Asp2046Asn	missense_variant	Exon 84 of 88	5	NM_001393982.1	ENSP00000295246.7	A0A8J8YUB5
ANKRD36C	ENST00000612359.4 link	c.190G>A	p.Asp64Asn	missense_variant	Exon 2 of 6	1		ENSP00000485004.1	A0A0C4DH05
ANKRD36C	ENST00000488721.5 link	n.1286G>A		non_coding_transcript_exon_variant	Exon 4 of 4	1
ANKRD36C	ENST00000456556.5 link	c.5113G>A	p.Asp1705Asn	missense_variant	Exon 64 of 67	5		ENSP00000403302.1	Q5JPF3-1

Frequencies

GnomAD3 genomes

AF:

0.00500

AC:

760

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.00764

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00818

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00544

AC:

1066

AN:

196092

Hom.:

AF XY:

0.00582

AC XY:

605

AN XY:

103952

show subpopulations

Gnomad AFR exome

AF:

0.00115

Gnomad AMR exome

AF:

0.00216

Gnomad ASJ exome

AF:

0.000218

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00525

Gnomad FIN exome

AF:

0.00694

Gnomad NFE exome

AF:

0.00844

Gnomad OTH exome

AF:

0.00667

GnomAD4 exome

AF:

0.00785

AC:

11324

AN:

1442542

Hom.:

Cov.:

AF XY:

0.00784

AC XY:

5611

AN XY:

715792

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00198

Gnomad4 ASJ exome

AF:

0.000232

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00599

Gnomad4 FIN exome

AF:

0.00702

Gnomad4 NFE exome

AF:

0.00894

Gnomad4 OTH exome

AF:

0.00758

GnomAD4 genome

AF:

0.00499

AC:

760

AN:

152196

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

375

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00540

Gnomad4 FIN

AF:

0.00764

Gnomad4 NFE

AF:

0.00818

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00709

Hom.:

Bravo

AF:

0.00432

ExAC

AF:

0.00455

AC:

548

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANKRD36C: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0091

.;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.51

T;T

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-1.0

PROVEAN

Uncertain

-3.3

.;D

REVEL

Benign

0.042

Sift

Benign

0.042

.;D

Sift4G

Pathogenic

0.0

D;T

Vest4

0.11

MVP

0.15

ClinPred

0.028

GERP RS

-0.10

Varity_R

0.13

gMVP

0.0066

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

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