Variant 10-5884030-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_019046.3(ANKRD16):c.626T>C(p.Leu209Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

ANKRD16
NM_019046.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ANKRD16	NM_019046.3 linkuse as main transcript	c.626T>C	p.Leu209Ser	missense_variant	4/8	ENST00000380094.10
ANKRD16	NM_001009941.3 linkuse as main transcript	c.626T>C	p.Leu209Ser	missense_variant	4/7
ANKRD16	NM_001009943.3 linkuse as main transcript	c.626T>C	p.Leu209Ser	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD16	ENST00000380094.10 linkuse as main transcript	c.626T>C	p.Leu209Ser	missense_variant	4/8	2	NM_019046.3	P1	Q6P6B7-1
ANKRD16	ENST00000380092.8 linkuse as main transcript	c.626T>C	p.Leu209Ser	missense_variant	4/7	1		P1	Q6P6B7-1
ANKRD16	ENST00000191063.8 linkuse as main transcript	c.626T>C	p.Leu209Ser	missense_variant	4/6	3			Q6P6B7-2
ANKRD16	ENST00000492368.1 linkuse as main transcript	n.215T>C		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Aug 17, 2022

The c.626T>C (p.L209S) alteration is located in exon 4 (coding exon 4) of the ANKRD16 gene. This alteration results from a T to C substitution at nucleotide position 626, causing the leucine (L) at amino acid position 209 to be replaced by a serine (S). 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

0.70

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

T;T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

.;T;T

M_CAP

Pathogenic

0.57

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Uncertain

0.37

MutationAssessor

Pathogenic

3.7

H;H;H

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.96

D;D;.

Vest4

0.61

MutPred

0.81

Gain of catalytic residue at L209 (P = 1e-04);Gain of catalytic residue at L209 (P = 1e-04);Gain of catalytic residue at L209 (P = 1e-04);

MVP

0.91

MPC

0.29

ClinPred

0.97

GERP RS

4.8

Varity_R

0.42

gMVP

0.75

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