dbSNP rs759699457: ELMOD3:c.-232-75_-232-72delAAAA (chr2-85356880-CAAAA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001135022.2(ELMOD3):c.-232-75_-232-72delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000674 in 14,846 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ELMOD3
NM_001135022.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.706

Publications

0 publications found

Variant links:

Genes affected

ELMOD3 (HGNC:26158): (ELMO domain containing 3) This gene encodes a member of the engulfment and cell motility family of GTPase-activating proteins that regulate Arf GTPase proteins. Members of this family are defined by a conserved engulfment and cell motility domain. In rat cochlea, the encoded protein is found in stereocilia, kinocilia and cuticular plate of developing hair cells suggesting a function for this protein in cochlear sensory cells. An allelic variant of this family has been associated with autosomal recessive nonsyndromic deafness-88 in humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ELMOD3 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive nonsyndromic hearing loss 88
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen

ELMOD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135022.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ELMOD3	NM_001135022.2	MANE Select	c.-232-75_-232-72delAAAA	intron	N/A	NP_001128494.1	Q96FG2-1
ELMOD3	NM_032213.5		c.-232-75_-232-72delAAAA	intron	N/A	NP_115589.2
ELMOD3	NM_001135021.2		c.-232-75_-232-72delAAAA	intron	N/A	NP_001128493.1	Q96FG2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ELMOD3	ENST00000409013.8	TSL:1 MANE Select	c.-232-75_-232-72delAAAA	intron	N/A	ENSP00000387139.3	Q96FG2-1
ELMOD3	ENST00000315658.11	TSL:1	c.-232-75_-232-72delAAAA	intron	N/A	ENSP00000318264.7	Q96FG2-6
ELMOD3	ENST00000393852.8	TSL:1	c.-232-75_-232-72delAAAA	intron	N/A	ENSP00000377434.4	Q96FG2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

125142

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000674

AC:

AN:

14846

Hom.:

AF XY:

0.00

AC XY:

AN XY:

7682

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

474

American (AMR)

AF:

0.00

AC:

AN:

486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

638

East Asian (EAS)

AF:

0.00

AC:

AN:

930

South Asian (SAS)

AF:

0.00

AC:

AN:

730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000996

AC:

AN:

10044

Other (OTH)

AF:

0.00

AC:

AN:

988

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

125142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

60026

African (AFR)

AF:

0.00

AC:

AN:

34276

American (AMR)

AF:

0.00

AC:

AN:

12314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3060

East Asian (EAS)

AF:

0.00

AC:

AN:

4434

South Asian (SAS)

AF:

0.00

AC:

AN:

4018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57206

Other (OTH)

AF:

0.00

AC:

AN:

1688

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over