chr14-50757704-T-G

Position:

• chr14-50757704-T-G

Variant summary

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

The NM_020921.4(NIN):​c.3326A>C​(p.Asp1109Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NIN NM_020921.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33

Genes affected

NIN (HGNC:14906): (ninein) This gene encodes one of the proteins important for centrosomal function. This protein is important for positioning and anchoring the microtubules minus-ends in epithelial cells. Localization of this protein to the centrosome requires three leucine zippers in the central coiled-coil domain. Multiple alternatively spliced transcript variants that encode different isoforms have been reported. [provided by RefSeq, Jul 2008]

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=0.0770407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIN	NM_020921.4	c.3326A>C	p.Asp1109Ala	missense_variant	18/31	ENST00000530997.7	NP_065972.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7	c.3326A>C	p.Asp1109Ala	missense_variant	18/31	5	NM_020921.4	ENSP00000436092.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 24, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.044	.;.;T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.93	D;.;D;D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.077	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;L;L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.7	N;.;N;N
REVEL	Benign	0.058
Sift	Uncertain	0.014	D;.;D;D
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.021	B;B;B;B
Vest4		0.24
MutPred		0.31		Gain of catalytic residue at L1108 (P = 0.0017);Gain of catalytic residue at L1108 (P = 0.0017);Gain of catalytic residue at L1108 (P = 0.0017);Gain of catalytic residue at L1108 (P = 0.0017);
MVP		0.28
MPC		0.26
ClinPred		0.17	T
GERP RS		3.5
Varity_R		0.052
gMVP		0.15

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

LitVar

Other links and lift over

dbSNP: rs797045742; hg19: chr14-51224422;