2-238102093-C-A

Variant summary

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

The NM_194312.4(ESPNL):​c.447C>A​(p.Asp149Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,288 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: 34)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ESPNL
NM_194312.4 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
Variant links:
Genes affected
ESPNL (HGNC:27937): (espin like) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament bundle assembly and sensory perception of sound. Predicted to be located in stereocilium tip. Predicted to be active in cytoplasm. [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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35139096).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESPNLNM_194312.4 linkc.447C>A p.Asp149Glu missense_variant Exon 2 of 9 ENST00000343063.8 NP_919288.2 Q6ZVH7-1B3KXY4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ESPNLENST00000343063.8 linkc.447C>A p.Asp149Glu missense_variant Exon 2 of 9 2 NM_194312.4 ENSP00000339115.3 Q6ZVH7-1
ESPNLENST00000409169.5 linkc.447C>A p.Asp149Glu missense_variant Exon 2 of 8 5 ENSP00000386577.1 Q6ZVH7-2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
7.05e-7
AC:
1
AN:
1418288
Hom.:
0
Cov.:
35
AF XY:
0.00000142
AC XY:
1
AN XY:
702118
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.16e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
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
Sep 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.447C>A (p.D149E) alteration is located in exon 2 (coding exon 2) of the ESPNL gene. This alteration results from a C to A substitution at nucleotide position 447, causing the aspartic acid (D) at amino acid position 149 to be replaced by a glutamic acid (E). 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
Uncertain
0.54
BayesDel_addAF
Benign
-0.086
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.027
T;.
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.68
T;T
M_CAP
Benign
0.081
D
MetaRNN
Benign
0.35
T;T
MetaSVM
Benign
-0.60
T
MutationAssessor
Benign
1.7
L;L
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-3.1
D;D
REVEL
Benign
0.28
Sift
Uncertain
0.013
D;D
Sift4G
Uncertain
0.025
D;D
Polyphen
0.98
D;.
Vest4
0.53
MutPred
0.52
Gain of disorder (P = 0.0745);Gain of disorder (P = 0.0745);
MVP
0.16
MPC
0.44
ClinPred
0.95
D
GERP RS
2.8
Varity_R
0.36
gMVP
0.14

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: rs1691498720; hg19: chr2-239010734; API