14-50729605-C-A

Variant names:

• chr14-50729605-C-A
• rs141405524
• NM_020921.4:c.5996G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020921.4(NIN):​c.5996G>T​(p.Arg1999Leu) 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. 15/22 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. R1999H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NIN NM_020921.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 7 publications found

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]

NIN Gene-Disease associations (from GenCC):

• Seckel syndrome 7

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08292326).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020921.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	NM_020921.4	MANE Select	c.5996G>T	p.Arg1999Leu	missense	Exon 29 of 31	NP_065972.4
	NIN	NM_182946.2		c.5996G>T	p.Arg1999Leu	missense	Exon 29 of 30	NP_891991.2
	NIN	NM_182944.3		c.5996G>T	p.Arg1999Leu	missense	Exon 29 of 30	NP_891989.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	ENST00000530997.7	TSL:5 MANE Select	c.5996G>T	p.Arg1999Leu	missense	Exon 29 of 31	ENSP00000436092.2
	NIN	ENST00000382041.7	TSL:1	c.5996G>T	p.Arg1999Leu	missense	Exon 29 of 30	ENSP00000371472.3
	NIN	ENST00000382043.8	TSL:1	c.3857G>T	p.Arg1286Leu	missense	Exon 27 of 28	ENSP00000371474.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.4
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.035
Sift	Benign	0.094	T
Sift4G	Benign	0.068	T
Polyphen		0.047	B
Vest4		0.23
MutPred		0.21		Loss of MoRF binding (P = 0.0145)
MVP		0.30
MPC		0.16
ClinPred		0.29	T
GERP RS		2.9
Varity_R		0.045
gMVP		0.093
Mutation Taster		=96/4	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: rs141405524; hg19: chr14-51196323;