rs1240875389

Variant names:

• chr1-6425007-C-G
• rs1240875389
• NM_031475.3:c.52C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-6425007-C-G
• chr1-6425007-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_031475.3(ESPN):​c.52C>G​(p.Leu18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,315,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L18L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ESPN NM_031475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.35127926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESPN	NM_031475.3	c.52C>G	p.Leu18Val	missense_variant	Exon 1 of 13	ENST00000645284.1	NP_113663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESPN	ENST00000645284.1	c.52C>G	p.Leu18Val	missense_variant	Exon 1 of 13		NM_031475.3	ENSP00000496593.1
ESPN	ENST00000636330.1	c.52C>G	p.Leu18Val	missense_variant	Exon 1 of 11	5		ENSP00000490186.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000137 AC: 18 AN: 1315806 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 9 AN XY: 648718

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: 0.0000172

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	Benign	0.34
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.083	T;T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	.;T;T
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.47	N;.;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.1	.;.;N
REVEL	Benign	0.23
Sift	Benign	0.44	.;.;T
Sift4G	Pathogenic	0.0	.;.;D
Polyphen		1.0	D;.;D
Vest4		0.42
MutPred		0.44		Loss of disorder (P = 0.0839);Loss of disorder (P = 0.0839);Loss of disorder (P = 0.0839);
MVP		0.36
MPC		0.46
ClinPred		0.84	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1240875389; hg19: chr1-6485067;