rs1038291674

Variant summary

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

The NM_031475.3(ESPN):​c.97G>A​(p.Asp33Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,317,360 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D33Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ESPN
NM_031475.3 missense

Scores

3
8
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.01
Variant links:
Genes affected
ESPN (HGNC:13281): (espin) This gene encodes a multifunctional actin-bundling protein. It plays a major role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Mutations in this gene are associated with autosomal recessive neurosensory deafness, and autosomal dominant sensorineural deafness without vestibular involvement. [provided by RefSeq, Nov 2009]

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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
ESPNNM_031475.3 linkc.97G>A p.Asp33Asn missense_variant Exon 1 of 13 ENST00000645284.1 NP_113663.2 B1AK53-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ESPNENST00000645284.1 linkc.97G>A p.Asp33Asn missense_variant Exon 1 of 13 NM_031475.3 ENSP00000496593.1 B1AK53-1
ESPNENST00000636330.1 linkc.97G>A p.Asp33Asn missense_variant Exon 1 of 11 5 ENSP00000490186.1 A0A1B0GUN9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000152
AC:
2
AN:
1317360
Hom.:
0
Cov.:
31
AF XY:
0.00000154
AC XY:
1
AN XY:
649436
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:
0.00000191
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;T;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.85
.;D;D
M_CAP
Uncertain
0.24
D
MetaRNN
Uncertain
0.60
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L;.;L
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-3.7
.;.;D
REVEL
Uncertain
0.35
Sift
Benign
0.071
.;.;T
Sift4G
Pathogenic
0.0
.;.;D
Polyphen
1.0
D;.;D
Vest4
0.28
MutPred
0.46
Loss of disorder (P = 0.1004);Loss of disorder (P = 0.1004);Loss of disorder (P = 0.1004);
MVP
0.29
MPC
0.62
ClinPred
0.99
D
GERP RS
4.0
Varity_R
0.35
gMVP
0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-6485112; API