rs778646190

Variant names:

• chr6-64813571-T-C
• NM_001142800.2:c.3250A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-64813571-T-C
• chr6-64813571-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_001142800.2(EYS):​c.3250A>G​(p.Thr1084Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,392,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1084P) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: EYS NM_001142800.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271

Genes affected

EYS (HGNC:21555): (eyes shut homolog) The product of this gene contains multiple epidermal growth factor (EGF)-like and LamG domains. The protein is expressed in the photoreceptor layer of the retina, and the gene is mutated in autosomal recessive retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr6-64813571-T-G is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.09715372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYS	NM_001142800.2	c.3250A>G	p.Thr1084Ala	missense_variant	Exon 22 of 43	ENST00000503581.6	NP_001136272.1
EYS	NM_001292009.2	c.3250A>G	p.Thr1084Ala	missense_variant	Exon 22 of 44		NP_001278938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYS	ENST00000503581.6	c.3250A>G	p.Thr1084Ala	missense_variant	Exon 22 of 43	5	NM_001142800.2	ENSP00000424243.1
EYS	ENST00000370621.7	c.3250A>G	p.Thr1084Ala	missense_variant	Exon 22 of 44	1		ENSP00000359655.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1392598 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 686916

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.42
DANN	Benign	0.20
DEOGEN2	Benign	0.057	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.28	T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.097	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.21	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.22
Sift	Benign	0.78	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0010	B;.
Vest4		0.052
MutPred		0.53		Loss of methylation at K1079 (P = 0.1001);Loss of methylation at K1079 (P = 0.1001);
MVP		0.12
MPC		0.011
ClinPred		0.027	T
GERP RS		-0.12
Varity_R		0.039
gMVP		0.25

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: chr6-65523464;