Genetic Variant NHSL2:n.438C>T (chrX-72159919-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000623354.1(NHSL2):n.438C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000394 in 1,190,297 control chromosomes in the GnomAD database, including 1 homozygotes. There are 141 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.00041 ( 0 hom. 137 hem. )

Consequence

NHSL2
ENST00000623354.1 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.915

Variant links:

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]

NHSL2 links:

TPT1P15 (HGNC:55881): (TPT1 pseudogene 15)

TPT1P15 links:

LOC121627959 (HGNC:):

LOC121627959 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant X-72159919-C-T is Benign according to our data. Variant chrX-72159919-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660906.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC121627959		n.72159919C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NHSL2	ENST00000623354.1 link	n.438C>T		non_coding_transcript_exon_variant	Exon 2 of 2	1
TPT1P15	ENST00000432517.1 link	n.75C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.000286

AC:

AN:

112081

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34259

show subpopulations

Gnomad AFR

AF:

0.000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00264

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000300

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000430

AC:

AN:

181529

Hom.:

AF XY:

0.000448

AC XY:

AN XY:

66945

show subpopulations

Gnomad AFR exome

AF:

0.000321

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00565

Gnomad EAS exome

AF:

0.000145

Gnomad SAS exome

AF:

0.000106

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000295

Gnomad OTH exome

AF:

0.000675

GnomAD4 exome

AF:

0.000405

AC:

437

AN:

1078216

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

137

AN XY:

352132

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.0000290

Gnomad4 ASJ exome

AF:

0.00492

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000557

Gnomad4 FIN exome

AF:

0.0000260

Gnomad4 NFE exome

AF:

0.000369

Gnomad4 OTH exome

AF:

0.000583

GnomAD4 genome

AF:

0.000286

AC:

AN:

112081

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34259

show subpopulations

Gnomad4 AFR

AF:

0.000291

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00264

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000300

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000998

Hom.:

Bravo

AF:

0.000336

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FLJ44635: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.2

DANN

Benign

0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over