chr14-50725990-C-G

Position:

• chr14-50725990-C-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.6155G>C​(p.Arg2052Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 3.73

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=0.19643006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIN	NM_020921.4	c.6155G>C	p.Arg2052Thr	missense_variant	30/31	ENST00000530997.7	NP_065972.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7	c.6155G>C	p.Arg2052Thr	missense_variant	30/31	5	NM_020921.4	ENSP00000436092	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Ambry Genetics

Nov 10, 2022

The c.6155G>C (p.R2052T) alteration is located in exon 30 (coding exon 28) of the NIN gene. This alteration results from a G to C substitution at nucleotide position 6155, causing the arginine (R) at amino acid position 2052 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.083	.;.;.;.;T
Eigen	Benign	0.058
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D;.;.;D;D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;.;.;L
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.4	N;.;N;.;N
REVEL	Benign	0.044
Sift	Benign	0.31	T;.;D;.;D
Sift4G	Uncertain	0.046	D;D;T;T;D
Polyphen		0.33	B;B;.;.;B
Vest4		0.51
MutPred		0.30		Loss of MoRF binding (P = 0.0276);Loss of MoRF binding (P = 0.0276);.;.;Loss of MoRF binding (P = 0.0276);
MVP		0.42
MPC		0.23
ClinPred		0.66	D
GERP RS		5.0
Varity_R		0.18
gMVP		0.21

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: chr14-51192708;