chr14-50743529-A-C

Variant names:

• chr14-50743529-A-C
• NM_020921.4:c.5188T>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.5188T>G​(p.Leu1730Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NIN NM_020921.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001048
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528

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=0.14577773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIN	NM_020921.4	c.5188T>G	p.Leu1730Val	missense_variant, splice_region_variant	Exon 24 of 31	ENST00000530997.7	NP_065972.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIN	ENST00000530997.7	c.5188T>G	p.Leu1730Val	missense_variant, splice_region_variant	Exon 24 of 31	5	NM_020921.4	ENSP00000436092.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454388 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 724052

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.38
DEOGEN2	Benign	0.031	.;.;.;.;T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.82	T;.;.;T;T;T
MetaRNN	Benign	0.15	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.84	L;L;.;.;L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.55	N;.;N;.;N;N
REVEL	Benign	0.17
Sift	Benign	0.39	T;.;T;.;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		1.0	D;D;.;.;D;B
Vest4		0.13
MutPred		0.11		Gain of methylation at K1729 (P = 0.0486);Gain of methylation at K1729 (P = 0.0486);.;.;Gain of methylation at K1729 (P = 0.0486);Gain of methylation at K1729 (P = 0.0486);
MVP		0.60
MPC		0.14
ClinPred		0.057	T
GERP RS		-3.5
Varity_R		0.036
gMVP		0.029

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.064
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: chr14-51210247;