14-50757940-T-C

Variant names:

• chr14-50757940-T-C
• rs2073348
• NM_020921.4:c.3090A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020921.4(NIN):​c.3090A>G​(p.Ser1030Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1030S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NIN NM_020921.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919
• Publications: 18 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.011).
• BP7: Synonymous conserved (PhyloP=-0.919 with no splicing effect.

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.3090A>G	p.Ser1030Ser	synonymous	Exon 18 of 31	NP_065972.4
	NIN	NM_182946.2		c.3090A>G	p.Ser1030Ser	synonymous	Exon 18 of 30	NP_891991.2
	NIN	NM_182944.3		c.3090A>G	p.Ser1030Ser	synonymous	Exon 18 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.3090A>G	p.Ser1030Ser	synonymous	Exon 18 of 31	ENSP00000436092.2
	NIN	ENST00000382041.7	TSL:1	c.3090A>G	p.Ser1030Ser	synonymous	Exon 18 of 30	ENSP00000371472.3
	NIN	ENST00000382043.8	TSL:1	c.2399+1917A>G		intron	N/A	ENSP00000371474.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1840

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.57
PhyloP100		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2073348; hg19: chr14-51224658;