chrX-17375820-C-G

Variant names:

• chrX-17375820-C-G
• rs1435156319
• NM_001291867.2:c.63C>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001291867.2(NHS):​c.63C>G​(p.Pro21Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 112,440 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
• Consequence: NHS NM_001291867.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.28 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHS	NM_001291867.2	c.63C>G	p.Pro21Pro	synonymous_variant	Exon 1 of 9	ENST00000676302.1	NP_001278796.1
NHS	NM_198270.4	c.63C>G	p.Pro21Pro	synonymous_variant	Exon 1 of 8		NP_938011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1	c.63C>G	p.Pro21Pro	synonymous_variant	Exon 1 of 9		NM_001291867.2	ENSP00000502262.1
NHS	ENST00000380060.7	c.63C>G	p.Pro21Pro	synonymous_variant	Exon 1 of 8	1		ENSP00000369400.3

Frequencies

GnomAD3 genomes AF: 0.00000889 AC: 1 AN: 112440 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34656

Gnomad AFR AF: 0.0000322

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 Cov.: 31

GnomAD4 genome AF: 0.00000889 AC: 1 AN: 112440 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34656

Gnomad4 AFR AF: 0.0000322

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.8
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs1435156319; hg19: chrX-17393943;