Variant chr10-5889127-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_019046.3(ANKRD16):c.228C>G(p.His76Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,597,680 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 1 hom. )

Consequence

ANKRD16
NM_019046.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.492

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ANKRD16	NM_019046.3 linkuse as main transcript	c.228C>G	p.His76Gln	missense_variant	1/8	ENST00000380094.10
ANKRD16	NM_001009941.3 linkuse as main transcript	c.228C>G	p.His76Gln	missense_variant	1/7
ANKRD16	NM_001009943.3 linkuse as main transcript	c.228C>G	p.His76Gln	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD16	ENST00000380094.10 linkuse as main transcript	c.228C>G	p.His76Gln	missense_variant	1/8	2	NM_019046.3	P1	Q6P6B7-1
ANKRD16	ENST00000380092.8 linkuse as main transcript	c.228C>G	p.His76Gln	missense_variant	1/7	1		P1	Q6P6B7-1
ANKRD16	ENST00000191063.8 linkuse as main transcript	c.228C>G	p.His76Gln	missense_variant	1/6	3			Q6P6B7-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152054

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:

0.000831

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000611

AC:

AN:

229226

Hom.:

AF XY:

0.0000870

AC XY:

AN XY:

126434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000463

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000214

AC:

AN:

1445626

Hom.:

Cov.:

AF XY:

0.0000292

AC XY:

AN XY:

719622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000337

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74284

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:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000413

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 09, 2021

The c.228C>G (p.H76Q) alteration is located in exon 1 (coding exon 1) of the ANKRD16 gene. This alteration results from a C to G substitution at nucleotide position 228, causing the histidine (H) at amino acid position 76 to be replaced by a glutamine (Q). 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

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.92

.;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.81

D;D;D

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.0

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-7.9

D;D;D

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.012

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.87

MutPred

0.74

Gain of ubiquitination at K72 (P = 0.1008);Gain of ubiquitination at K72 (P = 0.1008);Gain of ubiquitination at K72 (P = 0.1008);

MVP

0.71

MPC

0.75

ClinPred

0.89

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.95

gMVP

0.72

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