Genetic Variant ELMOD3:c.-232-74_-232-72dupAAA (chr2-85356880-C-CAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001135022.2(ELMOD3):c.-232-74_-232-72dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000714 in 140,000 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 0.000048 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.-232-74_-232-72dupAAA	intron	N/A	NP_001128494.1	Q96FG2-1
ELMOD3	NM_032213.5		c.-232-74_-232-72dupAAA	intron	N/A	NP_115589.2
ELMOD3	NM_001135021.2		c.-232-74_-232-72dupAAA	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.-232-74_-232-72dupAAA	intron	N/A	ENSP00000387139.3	Q96FG2-1
ELMOD3	ENST00000315658.11	TSL:1	c.-232-74_-232-72dupAAA	intron	N/A	ENSP00000318264.7	Q96FG2-6
ELMOD3	ENST00000393852.8	TSL:1	c.-232-74_-232-72dupAAA	intron	N/A	ENSP00000377434.4	Q96FG2-1

Frequencies

GnomAD3 genomes

AF:

0.0000400

AC:

AN:

125138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

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:

0.000270

AC:

AN:

14842

Hom.:

Cov.:

AF XY:

0.000260

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:

0.00211

AC:

AN:

474

American (AMR)

AF:

0.00

AC:

AN:

486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

638

East Asian (EAS)

AF:

0.00215

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:

10040

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: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000479

AC:

AN:

125158

Hom.:

Cov.:

AF XY:

0.0000499

AC XY:

AN XY:

60068

show subpopulations

African (AFR)

AF:

0.000175

AC:

AN:

34342

American (AMR)

AF:

0.00

AC:

AN:

12322

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3060

East Asian (EAS)

AF:

0.00

AC:

AN:

4418

South Asian (SAS)

AF:

0.00

AC:

AN:

3996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57194

Other (OTH)

AF:

0.00

AC:

AN:

1702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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2-85356880-CAAAA-CAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over