7-16615892-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_020319.3(ANKMY2):​c.383G>T​(p.Cys128Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,611,224 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKMY2
NM_020319.3 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48
Variant links:
Genes affected
ANKMY2 (HGNC:25370): (ankyrin repeat and MYND domain containing 2) Predicted to enable enzyme binding activity and metal ion binding activity. Predicted to be located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKMY2NM_020319.3 linkc.383G>T p.Cys128Phe missense_variant Exon 5 of 10 ENST00000306999.7 NP_064715.1 Q8IV38A0A024R9Z6
LOC105375169XR_007060225.1 linkn.222-134C>A intron_variant Intron 2 of 4
LOC105375169XR_007060226.1 linkn.222-134C>A intron_variant Intron 2 of 4
LOC105375169XR_007060227.1 linkn.81-134C>A intron_variant Intron 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKMY2ENST00000306999.7 linkc.383G>T p.Cys128Phe missense_variant Exon 5 of 10 1 NM_020319.3 ENSP00000303570.2 Q8IV38
ANKMY2ENST00000628652.1 linkc.383G>T p.Cys128Phe missense_variant Exon 5 of 9 5 ENSP00000485738.1 G3V0G5
ANKMY2ENST00000447802.3 linkn.383G>T non_coding_transcript_exon_variant Exon 5 of 11 2 ENSP00000392259.1 G3V0G5
ENSG00000287799ENST00000663260.1 linkn.358-134C>A intron_variant Intron 3 of 3

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
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
GnomAD3 exomes
AF:
0.00000806
AC:
2
AN:
248158
Hom.:
0
AF XY:
0.00000745
AC XY:
1
AN XY:
134244
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.0000297
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459098
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725622
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.0000227
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152126
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.000145
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:
0.0000302
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 27, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.383G>T (p.C128F) alteration is located in exon 5 (coding exon 5) of the ANKMY2 gene. This alteration results from a G to T substitution at nucleotide position 383, causing the cysteine (C) at amino acid position 128 to be replaced by a phenylalanine (F). 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
0.97
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
30
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T;.
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.060
D
MetaRNN
Pathogenic
0.88
D;D
MetaSVM
Benign
-0.66
T
MutationAssessor
Uncertain
2.7
M;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-7.5
D;.
REVEL
Uncertain
0.55
Sift
Uncertain
0.0020
D;.
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
D;.
Vest4
0.91
MVP
0.93
MPC
0.36
ClinPred
0.99
D
GERP RS
5.8
Varity_R
0.92
gMVP
0.86

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.

Other links and lift over

dbSNP: rs368949494; hg19: chr7-16655517; API