rs1348024945

Variant names:

• chr6-63720598-A-C
• rs1348024945
• NM_001142800.2:c.9433T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-63720598-A-C
• chr6-63720598-A-G
• chr6-63720598-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001142800.2(EYS):​c.9433T>G​(p.Ter3145Gluext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000204 in 1,470,844 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 (★). Synonymous variant affecting the same amino acid position has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: EYS NM_001142800.2 stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.874
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001142800.2 Downstream stopcodon found after 7 codons.

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.9433T>G	p.Ter3145Gluext*?	stop_lost	Exon 43 of 43	NP_001136272.1	Q5T1H1-1
	PHF3	NM_001370348.2	MANE Select	c.*6890A>C		3_prime_UTR	Exon 16 of 16	NP_001357277.1	Q92576-1
	EYS	NM_001292009.2		c.9496T>G	p.Ter3166Gluext*?	stop_lost	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.9433T>G	p.Ter3145Gluext*?	stop_lost	Exon 43 of 43	ENSP00000424243.1	Q5T1H1-1
	EYS	ENST00000370621.7	TSL:1	c.9496T>G	p.Ter3166Gluext*?	stop_lost	Exon 44 of 44	ENSP00000359655.3	Q5T1H1-3
	PHF3	ENST00000262043.8	TSL:5 MANE Select	c.*6890A>C		3_prime_UTR	Exon 16 of 16	ENSP00000262043.4	Q92576-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1318690 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 645050

African (AFR) AF: 0.0000348 AC: 1 AN: 28774

American (AMR) AF: 0.00 AC: 0 AN: 24640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20570

East Asian (EAS) AF: 0.00 AC: 0 AN: 35174

South Asian (SAS) AF: 0.00 AC: 0 AN: 64826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038096

Other (OTH) AF: 0.0000183 AC: 1 AN: 54692

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152154 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74330

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5208

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.038
DANN	Benign	0.66
Eigen	Benign	-0.0024
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.049	N
PhyloP100		-0.87
Vest4		0.24
GERP RS		-2.2
Mutation Taster		=83/17	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: rs1348024945; hg19: chr6-64430494;