NM_001291867.2:c.216_218delGCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_001291867.2(NHS):c.216_218delGCC(p.Pro73del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00632 in 1,071,997 control chromosomes in the GnomAD database, including 297 homozygotes. There are 1,744 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 153 hom., 958 hem., cov: 21)

Exomes 𝑓: 0.0033 ( 144 hom. 786 hem. )

Consequence

NHS
NM_001291867.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.20

Publications

1 publications found

Variant links:

Genes affected

NHS (HGNC:7820): (NHS actin remodeling regulator) This gene encodes a protein containing four conserved nuclear localization signals. The encoded protein functions in eye, tooth, craniofacial and brain development, and it can regulate actin remodeling and cell morphology. Mutations in this gene have been shown to cause Nance-Horan syndrome, and also X-linked cataract-40. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2014]

NHS Gene-Disease associations (from GenCC):

Nance-Horan syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
early-onset nuclear cataract
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NHS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001291867.2

BP6

Variant X-17375961-ACCG-A is Benign according to our data. Variant chrX-17375961-ACCG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 96635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHS	NM_001291867.2 link	c.216_218delGCC	p.Pro73del	disruptive_inframe_deletion	Exon 1 of 9	ENST00000676302.1	NP_001278796.1	Q6T4R5-1
NHS	NM_198270.4 link	c.216_218delGCC	p.Pro73del	disruptive_inframe_deletion	Exon 1 of 8		NP_938011.1	Q6T4R5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1 link	c.216_218delGCC	p.Pro73del	disruptive_inframe_deletion	Exon 1 of 9		NM_001291867.2	ENSP00000502262.1		Q6T4R5-1
NHS	ENST00000380060.7 link	c.216_218delGCC	p.Pro73del	disruptive_inframe_deletion	Exon 1 of 8	1		ENSP00000369400.3		Q6T4R5-2

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

3570

AN:

110092

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00113

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00437

Gnomad NFE

AF:

0.000343

Gnomad OTH

AF:

0.0246

GnomAD2 exomes

AF:

0.00377

AC:

186

AN:

49359

AF XY:

0.00276

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.00690

Gnomad ASJ exome

AF:

0.000228

Gnomad EAS exome

AF:

0.00244

Gnomad FIN exome

AF:

0.000606

Gnomad NFE exome

AF:

0.000565

Gnomad OTH exome

AF:

0.00739

GnomAD4 exome

AF:

0.00333

AC:

3202

AN:

961861

Hom.:

144

AF XY:

0.00256

AC XY:

786

AN XY:

307081

show subpopulations

African (AFR)

AF:

0.121

AC:

2478

AN:

20504

American (AMR)

AF:

0.00977

AC:

190

AN:

19457

Ashkenazi Jewish (ASJ)

AF:

0.000125

AC:

AN:

15986

East Asian (EAS)

AF:

0.0000988

AC:

AN:

20244

South Asian (SAS)

AF:

0.000840

AC:

AN:

40491

European-Finnish (FIN)

AF:

0.000210

AC:

AN:

23828

Middle Eastern (MID)

AF:

0.00700

AC:

AN:

2571

European-Non Finnish (NFE)

AF:

0.000152

AC:

118

AN:

778856

Other (OTH)

AF:

0.00889

AC:

355

AN:

39924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

102

204

306

408

510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0325

AC:

3577

AN:

110136

Hom.:

153

Cov.:

AF XY:

0.0290

AC XY:

958

AN XY:

33006

show subpopulations

African (AFR)

AF:

0.110

AC:

3350

AN:

30363

American (AMR)

AF:

0.0159

AC:

169

AN:

10608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2610

East Asian (EAS)

AF:

0.00

AC:

AN:

3414

South Asian (SAS)

AF:

0.00113

AC:

AN:

2648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5729

Middle Eastern (MID)

AF:

0.00481

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.000344

AC:

AN:

52397

Other (OTH)

AF:

0.0243

AC:

AN:

1484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

112

224

337

449

561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00694

Hom.:

Asia WGS

AF:

0.00592

AC:

AN:

2375

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Mar 03, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 26, 2014

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 25, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Nance-Horan syndrome

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=88/12

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over