NM_001563.4:c.2377G>T

Variant names:

• chr6-75922106-C-A
• rs76604824
• NM_001563.4:c.2377G>T

Variant summary

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

The NM_001563.4(IMPG1):​c.2377G>T​(p.Asp793Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000836 in 1,196,222 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: 32)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: IMPG1 NM_001563.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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 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=0.14011097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPG1	NM_001563.4	c.2377G>T	p.Asp793Tyr	missense_variant	Exon 17 of 17	ENST00000369950.8	NP_001554.2
IMPG1	NM_001282368.2	c.2143G>T	p.Asp715Tyr	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.2377G>T	p.Asp793Tyr	missense_variant	Exon 17 of 17	1	NM_001563.4	ENSP00000358966.3
IMPG1	ENST00000611179.4	c.2143G>T	p.Asp715Tyr	missense_variant	Exon 16 of 16	5		ENSP00000481913.1
IMPG1	ENST00000369952.3	c.460G>T	p.Asp154Tyr	missense_variant	Exon 4 of 4	3		ENSP00000358968.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.36e-7 AC: 1 AN: 1196222 Hom.: 0 Cov.: 17 AF XY: 0.00000166 AC XY: 1 AN XY: 603986

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: 0.0000129

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	0.11
BayesDel_addAF	Benign	-0.0013	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D;.;D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.025	B;.;.
Vest4		0.31
MutPred		0.36		Loss of disorder (P = 0.0577);.;.;
MVP		0.32
MPC		0.091
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.21
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs76604824; hg19: chr6-76631823;