NM_001291867.2:c.127C>T

Variant names:

• chrX-17375884-C-T
• rs1486316948
• NM_001291867.2:c.127C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001291867.2(NHS):​c.127C>T​(p.Arg43Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000201 in 994,243 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000020 (0 hom. 1 hem.)
• Consequence: NHS NM_001291867.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18070182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHS	NM_001291867.2	c.127C>T	p.Arg43Trp	missense_variant	Exon 1 of 9	ENST00000676302.1	NP_001278796.1
NHS	NM_198270.4	c.127C>T	p.Arg43Trp	missense_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.127C>T	p.Arg43Trp	missense_variant	Exon 1 of 9		NM_001291867.2	ENSP00000502262.1
NHS	ENST00000380060.7	c.127C>T	p.Arg43Trp	missense_variant	Exon 1 of 8	1		ENSP00000369400.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000201 AC: 2 AN: 994243 Hom.: 0 Cov.: 31 AF XY: 0.00000313 AC XY: 1 AN XY: 319781

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000125

Gnomad4 OTH exome AF: 0.0000239

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.063
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.022	D
Vest4		0.25
MutPred		0.15		Loss of glycosylation at P41 (P = 0.1036);
MVP		0.14
MPC		0.73
ClinPred		0.66	D
GERP RS		3.3
gMVP		0.12

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: rs1486316948; hg19: chrX-17394007;