NM_033100.4:c.41T>A

Variant names:

• chr10-84194801-T-A
• NM_033100.4:c.41T>A

Variant summary

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

The NM_033100.4(CDHR1):​c.41T>A​(p.Leu14Gln) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDHR1 NM_033100.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.54

Genes affected

CDHR1 (HGNC:14550): (cadherin related family member 1) This gene belongs to the cadherin superfamily of calcium-dependent cell adhesion molecules. The encoded protein is a photoreceptor-specific cadherin that plays a role in outer segment disc morphogenesis. Mutations in this gene are associated with inherited retinal dystrophies. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 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=0.24253458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDHR1	NM_033100.4	c.41T>A	p.Leu14Gln	missense_variant	Exon 1 of 17	ENST00000623527.4	NP_149091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDHR1	ENST00000623527.4	c.41T>A	p.Leu14Gln	missense_variant	Exon 1 of 17	1	NM_033100.4	ENSP00000485478.1
CDHR1	ENST00000332904.7	c.41T>A	p.Leu14Gln	missense_variant	Exon 1 of 17	1		ENSP00000331063.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Cone-rod dystrophy 15 Uncertain:1

Feb 01, 2024

Department of Medical Genetics, Erciyes University Faculty of Medicine

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T;.
Eigen	Benign	-0.046
Eigen_PC	Benign	0.0077
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.66	T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.18
Sift	Uncertain	0.0040	.;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.61	P;P
Vest4		0.37
MutPred		0.52		Gain of sheet (P = 1e-04);Gain of sheet (P = 1e-04);
MVP		0.50
ClinPred		0.89	D
GERP RS		3.5
Varity_R		0.42
gMVP		0.60

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: chr10-85954557;