2-238101966-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_194312.4(ESPNL):​c.320C>T​(p.Pro107Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,609,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ESPNL
NM_194312.4 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESPNLNM_194312.4 linkc.320C>T p.Pro107Leu 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.320C>T p.Pro107Leu missense_variant Exon 2 of 9 2 NM_194312.4 ENSP00000339115.3 Q6ZVH7-1
ESPNLENST00000409169.5 linkc.320C>T p.Pro107Leu missense_variant Exon 2 of 8 5 ENSP00000386577.1 Q6ZVH7-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152190
Hom.:
0
Cov.:
34
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000330
AC:
8
AN:
242204
Hom.:
0
AF XY:
0.0000529
AC XY:
7
AN XY:
132236
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000292
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:
0.0000641
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000110
AC:
161
AN:
1457486
Hom.:
0
Cov.:
38
AF XY:
0.000106
AC XY:
77
AN XY:
725108
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
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:
0.000141
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152190
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74334
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000413
AC:
5
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.320C>T (p.P107L) alteration is located in exon 2 (coding exon 2) of the ESPNL gene. This alteration results from a C to T substitution at nucleotide position 320, causing the proline (P) at amino acid position 107 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
Benign
0.23
BayesDel_addAF
Benign
-0.048
T
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
T;.
Eigen
Uncertain
0.28
Eigen_PC
Benign
0.19
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.83
T;T
M_CAP
Pathogenic
0.32
D
MetaRNN
Uncertain
0.55
D;D
MetaSVM
Uncertain
0.018
D
MutationAssessor
Uncertain
2.2
M;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Uncertain
0.37
Sift
Benign
0.21
T;T
Sift4G
Benign
0.30
T;T
Polyphen
0.99
D;.
Vest4
0.55
MVP
0.65
MPC
0.16
ClinPred
0.49
T
GERP RS
4.5
Varity_R
0.24
gMVP
0.62

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: rs753585102; hg19: chr2-239010607; COSMIC: COSV54540928; COSMIC: COSV54540928; API