rs2073348

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-50757940-T-A
• chr14-50757940-T-C
• chr14-50757940-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_020921.4(NIN):​c.3090A>T​(p.Ser1030Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,613,906 control chromosomes in the GnomAD database, including 81,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7015 hom., cov: 32)
  • Exomes 𝑓: 0.31 (74001 hom.)
• Consequence: NIN NM_020921.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.013).
• BP6: Variant 14-50757940-T-A is Benign according to our data. Variant chr14-50757940-T-A is described in ClinVar as Benign. ClinVar VariationId is 129786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.919 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

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.3090A>T	p.Ser1030Ser	synonymous	Exon 18 of 31	NP_065972.4
	NIN	NM_182946.2		c.3090A>T	p.Ser1030Ser	synonymous	Exon 18 of 30	NP_891991.2	Q8N4C6-1
	NIN	NM_182944.3		c.3090A>T	p.Ser1030Ser	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.3090A>T	p.Ser1030Ser	synonymous	Exon 18 of 31	ENSP00000436092.2	Q8N4C6-7
	NIN	ENST00000382041.7	TSL:1	c.3090A>T	p.Ser1030Ser	synonymous	Exon 18 of 30	ENSP00000371472.3	Q8N4C6-1
	NIN	ENST00000382043.8	TSL:1	c.2399+1917A>T		intron	N/A	ENSP00000371474.4	Q8N4C6-11

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44258 AN: 151960 Hom.: 7003 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.292

GnomAD2 exomes AF: 0.336 AC: 84602 AN: 251454 AF XY: 0.328

Gnomad AFR exome AF: 0.189

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.510

Gnomad FIN exome AF: 0.309

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.314 AC: 458335 AN: 1461828 Hom.: 74001 Cov.: 50 AF XY: 0.310 AC XY: 225706 AN XY: 727224

African (AFR) AF: 0.185 AC: 6181 AN: 33478

American (AMR) AF: 0.485 AC: 21673 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 9347 AN: 26134

East Asian (EAS) AF: 0.496 AC: 19677 AN: 39700

South Asian (SAS) AF: 0.244 AC: 21006 AN: 86258

European-Finnish (FIN) AF: 0.303 AC: 16189 AN: 53410

Middle Eastern (MID) AF: 0.278 AC: 1604 AN: 5768

European-Non Finnish (NFE) AF: 0.309 AC: 343560 AN: 1111962

Other (OTH) AF: 0.316 AC: 19098 AN: 60396

GnomAD4 genome AF: 0.291 AC: 44283 AN: 152078 Hom.: 7015 Cov.: 32 AF XY: 0.295 AC XY: 21940 AN XY: 74334

African (AFR) AF: 0.194 AC: 8063 AN: 41494

American (AMR) AF: 0.406 AC: 6205 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1233 AN: 3472

East Asian (EAS) AF: 0.505 AC: 2607 AN: 5162

South Asian (SAS) AF: 0.241 AC: 1164 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3281 AN: 10582

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20842 AN: 67956

Other (OTH) AF: 0.289 AC: 610 AN: 2108

Alfa AF: 0.269 Hom.: 1840

Bravo AF: 0.299

Asia WGS AF: 0.316 AC: 1100 AN: 3478

EpiCase AF: 0.310

EpiControl AF: 0.309

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.57
DANN	Benign	0.54
PhyloP100		-0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV55380503;