12-96944774-A-C

Variant names:

• chr12-96944774-A-C
• rs781342056
• NM_152905.4:c.1633A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152905.4(NEDD1):​c.1633A>C​(p.Ile545Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I545V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEDD1 NM_152905.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

Genes affected

NEDD1 (HGNC:7723): (NEDD1 gamma-tubulin ring complex targeting factor) Predicted to be involved in protein localization to centrosome. Located in centrosome; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038895875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD1	NM_152905.4	c.1633A>C	p.Ile545Leu	missense_variant	Exon 13 of 16	ENST00000266742.9	NP_690869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD1	ENST00000266742.9	c.1633A>C	p.Ile545Leu	missense_variant	Exon 13 of 16	2	NM_152905.4	ENSP00000266742.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.0
DANN	Benign	0.79
DEOGEN2	Benign	0.023	T;T;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.50	.;T;.;T;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.039	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.;.;.
PhyloP100		-0.12
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.37	N;N;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.32	T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T
Polyphen		0.0	B;B;.;.;.
Vest4		0.18
MutPred		0.12		Gain of catalytic residue at I545 (P = 0.0191);Gain of catalytic residue at I545 (P = 0.0191);.;.;.;
MVP		0.19
MPC		0.059
ClinPred		0.050	T
GERP RS		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.060
Mutation Taster		=100/0	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: rs781342056; hg19: chr12-97338552;