rs74594049

Variant names:

• chr14-50756635-A-G
• rs74594049
• NM_020921.4:c.4395T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_020921.4(NIN):​c.4395T>C​(p.Thr1465Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000889 in 1,558,830 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (6 hom.)
• Consequence: NIN NM_020921.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.269
• Publications: 1 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 14-50756635-A-G is Benign according to our data. Variant chr14-50756635-A-G is described in ClinVar as Benign. ClinVar VariationId is 435997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.269 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 10 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.4395T>C	p.Thr1465Thr	synonymous	Exon 18 of 31	NP_065972.4
	NIN	NM_182946.2		c.4395T>C	p.Thr1465Thr	synonymous	Exon 18 of 30	NP_891991.2	Q8N4C6-1
	NIN	NM_182944.3		c.4395T>C	p.Thr1465Thr	synonymous	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.4395T>C	p.Thr1465Thr	synonymous	Exon 18 of 31	ENSP00000436092.2	Q8N4C6-7
	NIN	ENST00000382041.7	TSL:1	c.4395T>C	p.Thr1465Thr	synonymous	Exon 18 of 30	ENSP00000371472.3	Q8N4C6-1
	NIN	ENST00000382043.8	TSL:1	c.2400-1768T>C		intron	N/A	ENSP00000371474.4	Q8N4C6-11

Frequencies

GnomAD3 genomes AF: 0.00473 AC: 719 AN: 152150 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

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: 0.0000735

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00132 AC: 216 AN: 163848 AF XY: 0.00112

Gnomad AFR exome AF: 0.0175

Gnomad AMR exome AF: 0.00130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000630

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.000476 AC: 669 AN: 1406562 Hom.: 6 Cov.: 30 AF XY: 0.000425 AC XY: 295 AN XY: 694610

African (AFR) AF: 0.0161 AC: 514 AN: 31970

American (AMR) AF: 0.00159 AC: 58 AN: 36452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25290

East Asian (EAS) AF: 0.00 AC: 0 AN: 36478

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49946

Middle Eastern (MID) AF: 0.000877 AC: 5 AN: 5702

European-Non Finnish (NFE) AF: 0.0000203 AC: 22 AN: 1082120

Other (OTH) AF: 0.00118 AC: 69 AN: 58300

GnomAD4 genome AF: 0.00471 AC: 717 AN: 152268 Hom.: 10 Cov.: 32 AF XY: 0.00459 AC XY: 342 AN XY: 74452

African (AFR) AF: 0.0157 AC: 653 AN: 41546

American (AMR) AF: 0.00307 AC: 47 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68016

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00229 Hom.: 4

Bravo AF: 0.00564

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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	-0.71
CADD	Benign	5.9
DANN	Benign	0.69
PhyloP100		-0.27
Mutation Taster		=100/0	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: rs74594049; hg19: chr14-51223353;