Genetic Variant NHS:p.Pro104_Ala115dup (chrX-17376059-A-AGGCGGCGCCCGCAGCCGGCGAGGCGTCCTCGGCGGC) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001291867.2(NHS):c.310_345dupCCCGCAGCCGGCGAGGCGTCCTCGGCGGCGGCGGCG(p.Pro104_Ala115dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000904 in 110,643 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

NHS
NM_001291867.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.62

Publications

0 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: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001291867.2

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291867.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHS	NM_001291867.2	MANE Select	c.310_345dupCCCGCAGCCGGCGAGGCGTCCTCGGCGGCGGCGGCG	p.Pro104_Ala115dup	conservative_inframe_insertion	Exon 1 of 9	NP_001278796.1
	NHS	NM_198270.4		c.310_345dupCCCGCAGCCGGCGAGGCGTCCTCGGCGGCGGCGGCG	p.Pro104_Ala115dup	conservative_inframe_insertion	Exon 1 of 8	NP_938011.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHS	ENST00000676302.1	MANE Select	c.310_345dupCCCGCAGCCGGCGAGGCGTCCTCGGCGGCGGCGGCG	p.Pro104_Ala115dup	conservative_inframe_insertion	Exon 1 of 9	ENSP00000502262.1
	NHS	ENST00000380060.7	TSL:1	c.310_345dupCCCGCAGCCGGCGAGGCGTCCTCGGCGGCGGCGGCG	p.Pro104_Ala115dup	conservative_inframe_insertion	Exon 1 of 8	ENSP00000369400.3

Frequencies

GnomAD3 genomes

AF:

0.00000904

AC:

AN:

110643

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

943530

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

298554

African (AFR)

AF:

0.00

AC:

AN:

19453

American (AMR)

AF:

0.00

AC:

AN:

11481

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14012

East Asian (EAS)

AF:

0.00

AC:

AN:

21566

South Asian (SAS)

AF:

0.00

AC:

AN:

35617

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23672

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2509

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

775704

Other (OTH)

AF:

0.00

AC:

AN:

39516

GnomAD4 genome

AF:

0.00000904

AC:

AN:

110643

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33327

show subpopulations

African (AFR)

AF:

0.0000327

AC:

AN:

30564

American (AMR)

AF:

0.00

AC:

AN:

10640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2617

East Asian (EAS)

AF:

0.00

AC:

AN:

3440

South Asian (SAS)

AF:

0.00

AC:

AN:

2661

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5805

Middle Eastern (MID)

AF:

0.00

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52524

Other (OTH)

AF:

0.00

AC:

AN:

1484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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X-17376059-AGGCGGCGCCCGCAGCCGGCGAGGCGTCCTCGGCGGC-AGGCGGCGCCCGCAGCCGGCGAGGCGTCCTCGGCGGCGGCGGCGCCCGCAGCCGGCGAGGCGTCCTCGGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over