rs576579238

Variant names:

• chr6-75922133-C-A
• rs576579238
• NM_001563.4:c.2350G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-75922133-C-A
• chr6-75922133-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001563.4(IMPG1):​c.2350G>T​(p.Val784Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IMPG1 NM_001563.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

Genes affected

IMPG1 (HGNC:6055): (interphotoreceptor matrix proteoglycan 1) This gene encodes a protein that is a major component of the retinal interphotoreceptor matrix. The encoded protein is a proteoglycan that is thought to play a role in maintaining viability of photoreceptor cells and in adhesion of the neural retina to the retinal pigment epithelium. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055028945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPG1	NM_001563.4	c.2350G>T	p.Val784Leu	missense_variant	Exon 17 of 17	ENST00000369950.8	NP_001554.2
IMPG1	NM_001282368.2	c.2116G>T	p.Val706Leu	missense_variant	Exon 16 of 16		NP_001269297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPG1	ENST00000369950.8	c.2350G>T	p.Val784Leu	missense_variant	Exon 17 of 17	1	NM_001563.4	ENSP00000358966.3
IMPG1	ENST00000611179.4	c.2116G>T	p.Val706Leu	missense_variant	Exon 16 of 16	5		ENSP00000481913.1
IMPG1	ENST00000369952.3	c.433G>T	p.Val145Leu	missense_variant	Exon 4 of 4	3		ENSP00000358968.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1257940 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 632246

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.028
DANN	Benign	0.46
DEOGEN2	Benign	0.0029	T;.;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.47	T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.95	N;.;N
REVEL	Benign	0.016
Sift	Benign	0.16	T;.;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.036
MutPred		0.18		Gain of sheet (P = 0.0221);.;.;
MVP		0.13
MPC		0.013
ClinPred		0.062	T
GERP RS		-8.0
Varity_R		0.054
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs576579238; hg19: chr6-76631850;