10-5878141-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019046.3(ANKRD16):​c.1075G>A​(p.Ala359Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.000034 ( 0 hom. )

Consequence

ANKRD16
NM_019046.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.19
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056865066).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD16NM_019046.3 linkc.1075G>A p.Ala359Thr missense_variant Exon 7 of 8 ENST00000380094.10 NP_061919.1 Q6P6B7-1
ANKRD16NM_001009941.3 linkc.1075G>A p.Ala359Thr missense_variant Exon 7 of 7 NP_001009941.1 Q6P6B7-1
ANKRD16NM_001009943.3 linkc.*81G>A 3_prime_UTR_variant Exon 6 of 6 NP_001009943.1 Q6P6B7-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD16ENST00000380094.10 linkc.1075G>A p.Ala359Thr missense_variant Exon 7 of 8 2 NM_019046.3 ENSP00000369436.4 Q6P6B7-1
ANKRD16ENST00000380092.8 linkc.1075G>A p.Ala359Thr missense_variant Exon 7 of 7 1 ENSP00000369434.4 Q6P6B7-1
ANKRD16ENST00000191063 linkc.*81G>A 3_prime_UTR_variant Exon 6 of 6 3 ENSP00000352361.6 Q6P6B7-2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152200
Hom.:
0
Cov.:
33
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:
0.0000439
AC:
11
AN:
250708
Hom.:
0
AF XY:
0.0000443
AC XY:
6
AN XY:
135470
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000618
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000342
AC:
50
AN:
1461444
Hom.:
0
Cov.:
29
AF XY:
0.0000385
AC XY:
28
AN XY:
727024
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152200
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74360
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
Bravo
AF:
0.0000264
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1075G>A (p.A359T) alteration is located in exon 7 (coding exon 7) of the ANKRD16 gene. This alteration results from a G to A substitution at nucleotide position 1075, causing the alanine (A) at amino acid position 359 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
0.069
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
0.49
DANN
Benign
0.75
DEOGEN2
Benign
0.00078
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.42
.;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.057
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.49
N;N
PrimateAI
Benign
0.19
T
PROVEAN
Benign
-0.25
N;N
REVEL
Benign
0.047
Sift
Benign
0.41
T;T
Sift4G
Benign
0.40
T;T
Polyphen
0.0010
B;B
Vest4
0.046
MutPred
0.25
Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);
MVP
0.39
MPC
0.18
ClinPred
0.035
T
GERP RS
1.3
Varity_R
0.020
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs772833678; hg19: chr10-5920104; API