dbSNP rs5905692: FTSJ1:c.*9+340T>C (chrX-48483367-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012280.4(FTSJ1):c.*9+340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 240,432 control chromosomes in the GnomAD database, including 13,224 homozygotes. There are 25,233 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.

Frequency

Genomes: 𝑓 0.38 ( 8242 hom., 12168 hem., cov: 22)

Exomes 𝑓: 0.33 ( 4982 hom. 13065 hem. )

Consequence

FTSJ1
NM_012280.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.63

Publications

9 publications found

Variant links:

Genes affected

FTSJ1 (HGNC:13254): (FtsJ RNA 2'-O-methyltransferase 1) This gene encodes a member of the methyltransferase superfamily. The encoded protein localizes to the nucleolus, binds to S-adenosylmethionine, and may be involved in the processing and modification of ribosomal RNA. Mutations in this gene are associated with cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

FTSJ1 Gene-Disease associations (from GenCC):

intellectual disability, X-linked 9
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
X-linked complex neurodevelopmental disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
non-syndromic X-linked intellectual disability
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

FTSJ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTSJ1	NM_012280.4 link	c.*9+340T>C		intron_variant	Intron 12 of 12	ENST00000348411.3	NP_036412.1	Q9UET6-1A0A024QYX5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTSJ1	ENST00000348411.3 link	c.*9+340T>C		intron_variant	Intron 12 of 12	1	NM_012280.4	ENSP00000326948.2		Q9UET6-1

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

42137

AN:

110795

Hom.:

8243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.762

Gnomad AMI

AF:

0.187

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.202

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.366

GnomAD4 exome

AF:

0.332

AC:

42982

AN:

129595

Hom.:

4982

Cov.:

AF XY:

0.481

AC XY:

13065

AN XY:

27157

show subpopulations

African (AFR)

AF:

0.801

AC:

4475

AN:

5586

American (AMR)

AF:

0.445

AC:

2579

AN:

5794

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

1063

AN:

3725

East Asian (EAS)

AF:

0.512

AC:

4166

AN:

8144

South Asian (SAS)

AF:

0.542

AC:

6105

AN:

11265

European-Finnish (FIN)

AF:

0.254

AC:

1499

AN:

5910

Middle Eastern (MID)

AF:

0.309

AC:

160

AN:

518

European-Non Finnish (NFE)

AF:

0.251

AC:

20313

AN:

80779

Other (OTH)

AF:

0.333

AC:

2622

AN:

7874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

969

1938

2908

3877

4846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.380

AC:

42156

AN:

110837

Hom.:

8242

Cov.:

AF XY:

0.368

AC XY:

12168

AN XY:

33107

show subpopulations

African (AFR)

AF:

0.761

AC:

23128

AN:

30374

American (AMR)

AF:

0.371

AC:

3838

AN:

10334

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

561

AN:

2641

East Asian (EAS)

AF:

0.468

AC:

1643

AN:

3509

South Asian (SAS)

AF:

0.353

AC:

939

AN:

2659

European-Finnish (FIN)

AF:

0.164

AC:

966

AN:

5873

Middle Eastern (MID)

AF:

0.203

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.195

AC:

10360

AN:

53038

Other (OTH)

AF:

0.364

AC:

549

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

712

1424

2136

2848

3560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.276

Hom.:

30187

Bravo

AF:

0.419

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.28

(source)

DANN

Benign

0.69

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over