14-50744304-T-G

Position:

• chr14-50744304-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.5126A>C​(p.Asn1709Thr) 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. 13/21 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)
• Consequence: NIN NM_020921.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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]

LOC124903313 (HGNC:):

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=0.24863148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIN	NM_020921.4	c.5126A>C	p.Asn1709Thr	missense_variant	23/31	ENST00000530997.7	NP_065972.4
LOC124903313	XR_007064161.1	n.319T>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7	c.5126A>C	p.Asn1709Thr	missense_variant	23/31	5	NM_020921.4	ENSP00000436092	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.0089	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	.;.;.;.;T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T;.;.;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.25	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M;.;.;M;.
MutationTaster	Benign	0.60	N;N;N;N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N;.;D;.;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D;.;T;.;D;D
Sift4G	Uncertain	0.011	D;D;T;T;D;D
Polyphen		1.0	D;D;.;.;D;D
Vest4		0.58
MutPred		0.15		Gain of phosphorylation at N1709 (P = 0.0677);Gain of phosphorylation at N1709 (P = 0.0677);.;.;Gain of phosphorylation at N1709 (P = 0.0677);Gain of phosphorylation at N1709 (P = 0.0677);
MVP		0.68
MPC		0.37
ClinPred		0.97	D
GERP RS		3.5
Varity_R		0.19
gMVP		0.31

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: rs387907308; hg19: chr14-51211022;