chrX-71911332-G-A

Variant names:

• chrX-71911332-G-A
• NM_001013627.3:c.245G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013627.3(NHSL2):​c.245G>A​(p.Arg82His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: NHSL2 NM_001013627.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 0 publications found

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]

ENSG00000300926 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15256274).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013627.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHSL2	NM_001013627.3	MANE Select	c.245G>A	p.Arg82His	missense	Exon 1 of 8	NP_001013649.2	Q5HYW2-1
	NHSL2	NM_001438805.1		c.245G>A	p.Arg82His	missense	Exon 1 of 9	NP_001425734.1
	NHSL2	NM_001438806.1		c.245G>A	p.Arg82His	missense	Exon 1 of 8	NP_001425735.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHSL2	ENST00000633930.2	TSL:5 MANE Select	c.245G>A	p.Arg82His	missense	Exon 1 of 8	ENSP00000488668.1	Q5HYW2-1
	ENSG00000300926	ENST00000775127.1		n.58+588C>T		intron	N/A
	ENSG00000300926	ENST00000775128.1		n.235+375C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 997347 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 311483

African (AFR) AF: 0.00 AC: 0 AN: 22573

American (AMR) AF: 0.00 AC: 0 AN: 24375

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17079

East Asian (EAS) AF: 0.00 AC: 0 AN: 24696

South Asian (SAS) AF: 0.00 AC: 0 AN: 44162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 794591

Other (OTH) AF: 0.00 AC: 0 AN: 42107

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.4
PrimateAI	Pathogenic	0.90	D
Sift4G	Benign	0.079	T
Vest4		0.11
MutPred		0.25		Loss of sheet (P = 0.0025)
GERP RS		3.2
PromoterAI		-0.16	Neutral
gMVP		0.11
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chrX-71131182;