X-71911307-C-T

Variant names:

• chrX-71911307-C-T
• rs946275942
• NM_001013627.3:c.220C>T

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.220C>T​(p.Arg74Cys) 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. 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. R74S) has been classified 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: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• 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=0.18778986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NHSL2	NM_001013627.3	c.220C>T	p.Arg74Cys	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.220C>T	p.Arg74Cys	missense_variant	Exon 1 of 8	5	NM_001013627.3	ENSP00000488668.1
ENSG00000300926	ENST00000775127.1	n.59-594G>A		intron_variant	Intron 1 of 2
ENSG00000300926	ENST00000775128.1	n.235+400G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000133 AC: 1 AN: 74948 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000203

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1014027 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 321559

African (AFR) AF: 0.00 AC: 0 AN: 23396

American (AMR) AF: 0.00 AC: 0 AN: 25892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17743

East Asian (EAS) AF: 0.00 AC: 0 AN: 25644

South Asian (SAS) AF: 0.00 AC: 0 AN: 46572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25101

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3309

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 803493

Other (OTH) AF: 0.00 AC: 0 AN: 42877

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.2
PrimateAI	Pathogenic	0.91	D
Sift4G	Uncertain	0.016	D
Vest4		0.33
MutPred		0.38		Gain of catalytic residue at L75 (P = 0.0112);
GERP RS		2.5
PromoterAI		0.0020	Neutral
gMVP		0.23
Mutation Taster		=89/11	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

dbSNP: rs946275942; hg19: chrX-71131157; COSMIC: COSV105941864;