Variant 10-5884034-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019046.3(ANKRD16):c.622G>A(p.Ala208Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000551 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A208P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

ANKRD16
NM_019046.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39278337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ANKRD16	NM_019046.3 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/8	ENST00000380094.10
ANKRD16	NM_001009941.3 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/7
ANKRD16	NM_001009943.3 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD16	ENST00000380094.10 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/8	2	NM_019046.3	P1	Q6P6B7-1
ANKRD16	ENST00000380092.8 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/7	1		P1	Q6P6B7-1
ANKRD16	ENST00000191063.8 linkuse as main transcript	c.622G>A	p.Ala208Thr	missense_variant	4/6	3			Q6P6B7-2
ANKRD16	ENST00000492368.1 linkuse as main transcript	n.211G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000955

AC:

AN:

251362

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000125

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000200

ExAC

AF:

0.0000165

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

Sep 25, 2023

The c.622G>A (p.A208T) alteration is located in exon 4 (coding exon 4) of the ANKRD16 gene. This alteration results from a G to A substitution at nucleotide position 622, causing the alanine (A) at amino acid position 208 to be replaced by a threonine (T). 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

0.28

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0049

T;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

.;D;D

M_CAP

Uncertain

0.096

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.3

M;M;M

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.46

N;N;N

REVEL

Uncertain

0.33

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.45

B;B;.

Vest4

0.31

MutPred

0.70

Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);

MVP

0.71

MPC

0.18

ClinPred

0.094

GERP RS

3.9

Varity_R

0.11

gMVP

0.57

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