NM_001135022.2:c.15T>C

Variant names:

• chr2-85357213-T-C
• NM_001135022.2:c.15T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001135022.2(ELMOD3):​c.15T>C​(p.Ser5Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELMOD3 NM_001135022.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.527
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 2-85357213-T-C is Benign according to our data. Variant chr2-85357213-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2015080.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.527 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD3	NM_001135022.2	MANE Select	c.15T>C	p.Ser5Ser	synonymous	Exon 4 of 14	NP_001128494.1	Q96FG2-1
	ELMOD3	NM_032213.5		c.15T>C	p.Ser5Ser	synonymous	Exon 2 of 11	NP_115589.2
	ELMOD3	NM_001135021.2		c.15T>C	p.Ser5Ser	synonymous	Exon 5 of 15	NP_001128493.1	Q96FG2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD3	ENST00000409013.8	TSL:1 MANE Select	c.15T>C	p.Ser5Ser	synonymous	Exon 4 of 14	ENSP00000387139.3	Q96FG2-1
	ELMOD3	ENST00000315658.11	TSL:1	c.15T>C	p.Ser5Ser	synonymous	Exon 2 of 11	ENSP00000318264.7	Q96FG2-6
	ELMOD3	ENST00000393852.8	TSL:1	c.15T>C	p.Ser5Ser	synonymous	Exon 3 of 13	ENSP00000377434.4	Q96FG2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.0
DANN	Benign	0.72
PhyloP100		0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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

hg19: chr2-85584336;