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

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2660906.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000623354.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHSL2	ENST00000623354.1	TSL:1	n.438C>T		non_coding_transcript_exon	Exon 2 of 2
	TPT1P15	ENST00000432517.1	TSL:6	n.75C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.000286

AC:

AN:

112081

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000430

AC:

AN:

181529

AF XY:

0.000448

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 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

African (AFR)

AF:

0.000269

AC:

AN:

26030

American (AMR)

AF:

0.0000290

AC:

AN:

34477

Ashkenazi Jewish (ASJ)

AF:

0.00492

AC:

AN:

18695

East Asian (EAS)

AF:

0.00

AC:

AN:

29329

South Asian (SAS)

AF:

0.0000557

AC:

AN:

53843

European-Finnish (FIN)

AF:

0.0000260

AC:

AN:

38422

Middle Eastern (MID)

AF:

0.000250

AC:

AN:

4006

European-Non Finnish (NFE)

AF:

0.000369

AC:

306

AN:

828789

Other (OTH)

AF:

0.000583

AC:

AN:

44625

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000286

AC:

AN:

112081

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34259

show subpopulations

African (AFR)

AF:

0.000291

AC:

AN:

30883

American (AMR)

AF:

0.00

AC:

AN:

10511

Ashkenazi Jewish (ASJ)

AF:

0.00264

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3562

South Asian (SAS)

AF:

0.00

AC:

AN:

2700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6073

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000300

AC:

AN:

53268

Other (OTH)

AF:

0.00

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000998

Hom.:

Bravo

AF:

0.000336

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.2

(source)

DANN

Benign

0.43

PhyloP100

0.92

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over