1-6441006-C-T

Variant names:

• chr1-6441006-C-T
• rs766939513
• NM_031475.3:c.931C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031475.3(ESPN):​c.931C>T​(p.Leu311Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000754 in 1,458,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: ESPN NM_031475.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87
• Publications: 0 publications found

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]

ESPN Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD, AR Classification: DEFINITIVE, LIMITED Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 36

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome, type 1M

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESPN	NM_031475.3	c.931C>T	p.Leu311Leu	synonymous_variant	Exon 5 of 13	ENST00000645284.1	NP_113663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESPN	ENST00000645284.1	c.931C>T	p.Leu311Leu	synonymous_variant	Exon 5 of 13		NM_031475.3	ENSP00000496593.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000125 AC: 3 AN: 240528 AF XY: 0.00000760

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1458032 Hom.: 0 Cov.: 35 AF XY: 0.0000124 AC XY: 9 AN XY: 725106

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.000128 AC: 11 AN: 85738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111260

Other (OTH) AF: 0.00 AC: 0 AN: 60166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		5.9
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs766939513; hg19: chr1-6501066;