Variant 10-5889078-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019046.3(ANKRD16):c.277C>T(p.Arg93Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000447 in 1,565,690 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ANKRD16
NM_019046.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.846

Variant links:

Genes affected

ANKRD16 (HGNC:23471): (ankyrin repeat domain 16) Predicted to be involved in tRNA modification. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ANKRD16	NM_019046.3 linkuse as main transcript	c.277C>T	p.Arg93Trp	missense_variant	1/8	ENST00000380094.10
ANKRD16	NM_001009941.3 linkuse as main transcript	c.277C>T	p.Arg93Trp	missense_variant	1/7
ANKRD16	NM_001009943.3 linkuse as main transcript	c.277C>T	p.Arg93Trp	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD16	ENST00000380094.10 linkuse as main transcript	c.277C>T	p.Arg93Trp	missense_variant	1/8	2	NM_019046.3	P1	Q6P6B7-1
ANKRD16	ENST00000380092.8 linkuse as main transcript	c.277C>T	p.Arg93Trp	missense_variant	1/7	1		P1	Q6P6B7-1
ANKRD16	ENST00000191063.8 linkuse as main transcript	c.277C>T	p.Arg93Trp	missense_variant	1/6	3			Q6P6B7-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152040

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000980

AC:

AN:

204176

Hom.:

AF XY:

0.0000175

AC XY:

AN XY:

113982

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000360

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000653

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000354

AC:

AN:

1413650

Hom.:

Cov.:

AF XY:

0.00000712

AC XY:

AN XY:

702486

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000261

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74258

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:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000684

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.277C>T (p.R93W) alteration is located in exon 1 (coding exon 1) of the ANKRD16 gene. This alteration results from a C to T substitution at nucleotide position 277, causing the arginine (R) at amino acid position 93 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.078

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.2

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.9

D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.38

MVP

0.70

MPC

0.70

ClinPred

0.98

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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