11-62612451-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153265.3(EML3):​c.7G>C​(p.Gly3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,310,676 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: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: EML3 NM_153265.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19326976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EML3	NM_153265.3	c.7G>C	p.Gly3Arg	missense_variant	Exon 1 of 22	ENST00000394773.7	NP_694997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EML3	ENST00000394773.7	c.7G>C	p.Gly3Arg	missense_variant	Exon 1 of 22	1	NM_153265.3	ENSP00000378254.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1310676 Hom.: 0 Cov.: 30 AF XY: 0.00000155 AC XY: 1 AN XY: 645906

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000418

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.54e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;.;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.024
Sift	Uncertain	0.0060	D;D;D
Sift4G	Benign	0.071	T;T;T
Polyphen		0.29	B;.;B
Vest4		0.17
MutPred		0.15		Gain of methylation at G3 (P = 0.0402);Gain of methylation at G3 (P = 0.0402);Gain of methylation at G3 (P = 0.0402);
MVP		0.49
MPC		0.15
ClinPred		0.50	D
GERP RS		2.1
Varity_R		0.15
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62379923;