14-50778793-C-T

Variant names:

• chr14-50778793-C-T
• rs547438612
• NM_020921.4:c.447G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_020921.4(NIN):​c.447G>A​(p.Thr149Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,614,040 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00066 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (29 hom.)
• Consequence: NIN NM_020921.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -3.75
• Publications: 0 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 14-50778793-C-T is Benign according to our data. Variant chr14-50778793-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 211614.
• BP7: Synonymous conserved (PhyloP=-3.76 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000657 (100/152232) while in subpopulation SAS AF = 0.0201 (97/4822). AF 95% confidence interval is 0.0169. There are 3 homozygotes in GnomAd4. There are 72 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR,Unknown gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	NM_020921.4	MANE Select	c.447G>A	p.Thr149Thr	synonymous	Exon 6 of 31	NP_065972.4
	NIN	NM_182946.2		c.447G>A	p.Thr149Thr	synonymous	Exon 6 of 30	NP_891991.2
	NIN	NM_182944.3		c.447G>A	p.Thr149Thr	synonymous	Exon 6 of 30	NP_891989.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	ENST00000530997.7	TSL:5 MANE Select	c.447G>A	p.Thr149Thr	synonymous	Exon 6 of 31	ENSP00000436092.2
	NIN	ENST00000382041.7	TSL:1	c.447G>A	p.Thr149Thr	synonymous	Exon 6 of 30	ENSP00000371472.3
	NIN	ENST00000382043.8	TSL:1	c.447G>A	p.Thr149Thr	synonymous	Exon 5 of 28	ENSP00000371474.4

Frequencies

GnomAD3 genomes AF: 0.000657 AC: 100 AN: 152114 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00250 AC: 628 AN: 251476 AF XY: 0.00319

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00117 AC: 1717 AN: 1461808 Hom.: 29 Cov.: 30 AF XY: 0.00163 AC XY: 1184 AN XY: 727216

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0184 AC: 1586 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1111958

Other (OTH) AF: 0.00146 AC: 88 AN: 60388

GnomAD4 genome AF: 0.000657 AC: 100 AN: 152232 Hom.: 3 Cov.: 32 AF XY: 0.000967 AC XY: 72 AN XY: 74434

African (AFR) AF: 0.0000241 AC: 1 AN: 41536

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000156 Hom.: 0

Bravo AF: 0.000132

Asia WGS AF: 0.0100 AC: 37 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.6
DANN	Benign	0.92
PhyloP100		-3.8
Mutation Taster		=94/6	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: rs547438612; hg19: chr14-51245511;