7-130399004-A-T

Variant names:

• chr7-130399004-A-T
• NM_018718.3:c.1009T>A

Variant summary

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

The NM_018718.3(CEP41):​c.1009T>A​(p.Ser337Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 6.8e-7 (0 hom.)
• Consequence: CEP41 NM_018718.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.151

Genes affected

CEP41 (HGNC:12370): (centrosomal protein 41) This gene encodes a centrosomal and microtubule-binding protein which is predicted to have two coiled-coil domains and a rhodanese domain. In human retinal pigment epithelial cells the protein localized to centrioles and cilia. Mutations in this gene have been associated with Joubert Syndrome 15; an autosomal recessive ciliopathy and neurological disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

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=0.07349908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP41	NM_018718.3	c.1009T>A	p.Ser337Thr	missense_variant	Exon 11 of 11	ENST00000223208.10	NP_061188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP41	ENST00000223208.10	c.1009T>A	p.Ser337Thr	missense_variant	Exon 11 of 11	1	NM_018718.3	ENSP00000223208.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461836 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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: 0.0000116

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	0.075
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.31
DEOGEN2	Benign	0.029	.;T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.41	N;N;N
REVEL	Benign	0.21
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0020, 0.0	.;B;B
Vest4		0.083
MutPred		0.15		.;Gain of sheet (P = 0.0477);.;
MVP		0.74
MPC		0.066
ClinPred		0.083	T
GERP RS		-1.6
Varity_R		0.036
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-130038845;