rs756078762

Variant names:

• chrX-71911121-C-A
• rs756078762
• NM_001013627.3:c.34C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-71911121-C-A
• chrX-71911121-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001013627.3(NHSL2):​c.34C>A​(p.Arg12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,097,023 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000030 (0 hom. 3 hem.)
• Consequence: NHSL2 NM_001013627.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.743

Genes affected

NHSL2 (HGNC:33737): (NHS like 2) Predicted to enable calcium ion binding activity. Predicted to be involved in cell differentiation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14922017).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHSL2	NM_001013627.3	c.34C>A	p.Arg12Ser	missense_variant	Exon 1 of 8	ENST00000633930.2	NP_001013649.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHSL2	ENST00000633930.2	c.34C>A	p.Arg12Ser	missense_variant	Exon 1 of 8	5	NM_001013627.3	ENSP00000488668.1

Frequencies

GnomAD3 genomes AF: 0.00000886 AC: 1 AN: 112838 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 35056

Gnomad AFR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000305 AC: 3 AN: 984185 Hom.: 0 Cov.: 29 AF XY: 0.00000967 AC XY: 3 AN XY: 310365

Gnomad4 AFR exome AF: 0.0000474

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000235

Gnomad4 FIN exome AF: 0.0000409

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000886 AC: 1 AN: 112838 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 35056

Gnomad4 AFR AF: 0.00

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: 0.0000188

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
AlphaMissense	Benign	0.33
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.86	D
Sift4G	Benign	0.43	T
Vest4		0.19
MutPred		0.32		Loss of MoRF binding (P = 0.0076);
GERP RS		4.1
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: rs756078762; hg19: chrX-71130971;