NM_198493.3:c.421T>C

Variant summary

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

The NM_198493.3(ANKRD45):​c.421T>C​(p.Phe141Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,850 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ANKRD45
NM_198493.3 missense

Scores

2
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03
Variant links:
Genes affected
ANKRD45 (HGNC:24786): (ankyrin repeat domain 45)

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=0.2775385).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD45NM_198493.3 linkc.421T>C p.Phe141Leu missense_variant Exon 3 of 6 ENST00000333279.3 NP_940895.1 Q5TZF3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD45ENST00000333279.3 linkc.421T>C p.Phe141Leu missense_variant Exon 3 of 6 1 NM_198493.3 ENSP00000331268.2 Q5TZF3-2
ENSG00000285777ENST00000648193.1 linkn.421T>C non_coding_transcript_exon_variant Exon 3 of 8 ENSP00000498204.1
ENSG00000289426ENST00000693292.1 linkn.322+8887A>G intron_variant Intron 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251328
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135824
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:
0.0000327
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:
1461850
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727224
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.421T>C (p.F141L) alteration is located in exon 3 (coding exon 2) of the ANKRD45 gene. This alteration results from a T to C substitution at nucleotide position 421, causing the phenylalanine (F) at amino acid position 141 to be replaced by a leucine (L). 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
0.95
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
23
DANN
Uncertain
1.0
Eigen
Benign
0.015
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-2.5
N
REVEL
Benign
0.14
Sift
Benign
0.25
T
Sift4G
Pathogenic
0.0
D
Vest4
0.55
MVP
0.66
MPC
0.18
ClinPred
0.69
D
GERP RS
5.4
Varity_R
0.28
gMVP
0.46

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: rs778031973; hg19: chr1-173616060; API