NM_001142800.2:c.*98A>G

Variant names:

• chr6-63720498-T-C
• rs886061663
• NM_001142800.2:c.*98A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001142800.2(EYS):​c.*98A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 831,600 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: EYS NM_001142800.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.157
• Publications: 0 publications found

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]

PHF3 (HGNC:8921): (PHD finger protein 3) This gene encodes a member of a PHD finger-containing gene family. This gene may function as a transcription factor and may be involved in glioblastomas development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142800.2. 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
	EYS	NM_001142800.2	MANE Select	c.*98A>G		3_prime_UTR	Exon 43 of 43	NP_001136272.1	Q5T1H1-1
	PHF3	NM_001370348.2	MANE Select	c.*6790T>C		3_prime_UTR	Exon 16 of 16	NP_001357277.1	Q92576-1
	EYS	NM_001292009.2		c.*98A>G		3_prime_UTR	Exon 44 of 44	NP_001278938.1	Q5T1H1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYS	ENST00000503581.6	TSL:5 MANE Select	c.*98A>G		3_prime_UTR	Exon 43 of 43	ENSP00000424243.1	Q5T1H1-1
	PHF3	ENST00000262043.8	TSL:5 MANE Select	c.*6790T>C		3_prime_UTR	Exon 16 of 16	ENSP00000262043.4	Q92576-1
	EYS	ENST00000370621.7	TSL:1	c.*98A>G		3_prime_UTR	Exon 44 of 44	ENSP00000359655.3	Q5T1H1-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152098 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 7 AN: 679502 Hom.: 0 Cov.: 9 AF XY: 0.0000145 AC XY: 5 AN XY: 343734

African (AFR) AF: 0.00 AC: 0 AN: 16110

American (AMR) AF: 0.00 AC: 0 AN: 14516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14854

East Asian (EAS) AF: 0.00 AC: 0 AN: 31046

South Asian (SAS) AF: 0.00 AC: 0 AN: 41852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2410

European-Non Finnish (NFE) AF: 0.0000144 AC: 7 AN: 485160

Other (OTH) AF: 0.00 AC: 0 AN: 32832

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152098 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74306

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinitis Pigmentosa, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.16

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: rs886061663; hg19: chr6-64430394;