rs192017781

Variant names:

• chr14-50757383-C-T
• rs192017781
• NM_020921.4:c.3647G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020921.4(NIN):​c.3647G>A​(p.Arg1216Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00051 (0 hom.)
• Consequence: NIN NM_020921.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:5
• Conservation: PhyloP100: 0.386
• Publications: 6 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024294227).

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.3647G>A	p.Arg1216Gln	missense	Exon 18 of 31	NP_065972.4
	NIN	NM_182946.2		c.3647G>A	p.Arg1216Gln	missense	Exon 18 of 30	NP_891991.2	Q8N4C6-1
	NIN	NM_182944.3		c.3647G>A	p.Arg1216Gln	missense	Exon 18 of 30	NP_891989.3	C9J066

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIN	ENST00000530997.7	TSL:5 MANE Select	c.3647G>A	p.Arg1216Gln	missense	Exon 18 of 31	ENSP00000436092.2	Q8N4C6-7
	NIN	ENST00000382041.7	TSL:1	c.3647G>A	p.Arg1216Gln	missense	Exon 18 of 30	ENSP00000371472.3	Q8N4C6-1
	NIN	ENST00000382043.8	TSL:1	c.2399+2474G>A		intron	N/A	ENSP00000371474.4	Q8N4C6-11

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152158 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000334 AC: 84 AN: 251128 AF XY: 0.000354

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000464

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000510 AC: 745 AN: 1461740 Hom.: 0 Cov.: 64 AF XY: 0.000484 AC XY: 352 AN XY: 727166

African (AFR) AF: 0.000120 AC: 4 AN: 33454

American (AMR) AF: 0.000470 AC: 21 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

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

European-Non Finnish (NFE) AF: 0.000601 AC: 668 AN: 1111986

Other (OTH) AF: 0.000712 AC: 43 AN: 60392

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152276 Hom.: 0 Cov.: 31 AF XY: 0.000363 AC XY: 27 AN XY: 74452

African (AFR) AF: 0.000385 AC: 16 AN: 41566

American (AMR) AF: 0.000523 AC: 8 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000474 Hom.: 1

Bravo AF: 0.000382

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000362 AC: 44

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	3	-	not specified (3)
-	2	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.035
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.39
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.058
Sift	Benign	0.17	T
Sift4G	Benign	0.45	T
Polyphen		0.34	B
Vest4		0.11
MVP		0.32
MPC		0.33
ClinPred		0.018	T
GERP RS		4.9
Varity_R		0.068
gMVP		0.074
Mutation Taster		=95/5	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: rs192017781; hg19: chr14-51224101; COSMIC: COSV55402482;