rs1024222583

Variant names:

• chr11-62612451-C-A
• rs1024222583
• NM_153265.3:c.7G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-62612451-C-A
• chr11-62612451-C-T
• chr11-62612451-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153265.3(EML3):​c.7G>T​(p.Gly3Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,310,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G3R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: EML3 NM_153265.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86
• Publications: 0 publications found

Genes affected

EML3 (HGNC:26666): (EMAP like 3) Predicted to enable microtubule binding activity. Involved in mitotic metaphase plate congression and regulation of mitotic spindle assembly. Located in several cellular components, including midbody; mitotic spindle microtubule; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ROM1 (HGNC:10254): (retinal outer segment membrane protein 1) This gene is a member of a photoreceptor-specific gene family and encodes an integral membrane protein found in the photoreceptor disk rim of the eye. This protein can form homodimers or can heterodimerize with another photoreceptor, retinal degeneration slow (RDS). It is essential for disk morphogenesis, and may also function as an adhesion molecule involved in the stabilization and compaction of outer segment disks or in the maintenance of the curvature of the rim. Certain defects in this gene have been associated with the degenerative eye disease retinitis pigmentosa. [provided by RefSeq, Jul 2008]

ROM1 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 7

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4007098).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153265.3. 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
	EML3	NM_153265.3	MANE Select	c.7G>T	p.Gly3Trp	missense	Exon 1 of 22	NP_694997.2	Q32P44-1
	EML3	NM_001300793.2		c.7G>T	p.Gly3Trp	missense	Exon 1 of 22	NP_001287722.1
	EML3	NM_001300794.2		c.7G>T	p.Gly3Trp	missense	Exon 1 of 22	NP_001287723.1	Q32P44-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EML3	ENST00000394773.7	TSL:1 MANE Select	c.7G>T	p.Gly3Trp	missense	Exon 1 of 22	ENSP00000378254.2	Q32P44-1
	EML3	ENST00000964792.1		c.7G>T	p.Gly3Trp	missense	Exon 1 of 23	ENSP00000634851.1
	EML3	ENST00000529309.5	TSL:2	c.7G>T	p.Gly3Trp	missense	Exon 1 of 22	ENSP00000434513.1	Q32P44-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1310676 Hom.: 0 Cov.: 30 AF XY: 0.00000310 AC XY: 2 AN XY: 645906

African (AFR) AF: 0.00 AC: 0 AN: 26258

American (AMR) AF: 0.00 AC: 0 AN: 23916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22562

East Asian (EAS) AF: 0.00 AC: 0 AN: 28134

South Asian (SAS) AF: 0.00 AC: 0 AN: 71310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32464

Middle Eastern (MID) AF: 0.000516 AC: 2 AN: 3876

European-Non Finnish (NFE) AF: 9.54e-7 AC: 1 AN: 1047772

Other (OTH) AF: 0.00 AC: 0 AN: 54384

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.087
Eigen_PC	Benign	0.019
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.25		Loss of relative solvent accessibility (P = 0.0676)
MVP		0.53
MPC		0.15
ClinPred		0.82	D
GERP RS		2.1
PromoterAI		0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.16
Mutation Taster		=86/14	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: rs1024222583; hg19: chr11-62379923;