rs78979358

Variant names:

• chrX-48479062-C-G
• rs78979358
• NM_012280.4:c.307C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012280.4(FTSJ1):​c.307C>G​(p.Gln103Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,205,974 control chromosomes in the GnomAD database, including 12 homozygotes. There are 381 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (6 hom., 167 hem., cov: 24)
  • Exomes 𝑓: 0.00069 (6 hom. 214 hem.)
• Consequence: FTSJ1 NM_012280.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.63
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004870981).
• BP6: Variant X-48479062-C-G is Benign according to our data. Variant chrX-48479062-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00581 (654/112611) while in subpopulation AFR AF = 0.0204 (632/31043). AF 95% confidence interval is 0.019. There are 6 homozygotes in GnomAd4. There are 167 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012280.4. 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
	FTSJ1	NM_012280.4	MANE Select	c.307C>G	p.Gln103Glu	missense	Exon 5 of 13	NP_036412.1	A0A024QYX5
	FTSJ1	NM_001441197.1		c.307C>G	p.Gln103Glu	missense	Exon 5 of 11	NP_001428126.1
	FTSJ1	NM_001441198.1		c.307C>G	p.Gln103Glu	missense	Exon 6 of 12	NP_001428127.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTSJ1	ENST00000348411.3	TSL:1 MANE Select	c.307C>G	p.Gln103Glu	missense	Exon 5 of 13	ENSP00000326948.2	Q9UET6-1
	FTSJ1	ENST00000898808.1		c.307C>G	p.Gln103Glu	missense	Exon 6 of 14	ENSP00000568867.1
	FTSJ1	ENST00000898812.1		c.307C>G	p.Gln103Glu	missense	Exon 5 of 13	ENSP00000568871.1

Frequencies

GnomAD3 genomes AF: 0.00579 AC: 652 AN: 112557 Hom.: 6 Cov.: 24

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000932

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00329

GnomAD2 exomes AF: 0.00166 AC: 304 AN: 183269 AF XY: 0.000945

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.000766

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000134

Gnomad OTH exome AF: 0.000663

GnomAD4 exome AF: 0.000686 AC: 750 AN: 1093363 Hom.: 6 Cov.: 29 AF XY: 0.000596 AC XY: 214 AN XY: 359023

African (AFR) AF: 0.0227 AC: 596 AN: 26300

American (AMR) AF: 0.000796 AC: 28 AN: 35191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19362

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.0000555 AC: 3 AN: 54036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40501

Middle Eastern (MID) AF: 0.00145 AC: 6 AN: 4124

European-Non Finnish (NFE) AF: 0.0000537 AC: 45 AN: 837709

Other (OTH) AF: 0.00157 AC: 72 AN: 45943

GnomAD4 genome AF: 0.00581 AC: 654 AN: 112611 Hom.: 6 Cov.: 24 AF XY: 0.00480 AC XY: 167 AN XY: 34783

African (AFR) AF: 0.0204 AC: 632 AN: 31043

American (AMR) AF: 0.000931 AC: 10 AN: 10740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3555

South Asian (SAS) AF: 0.00 AC: 0 AN: 2743

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000132 AC: 7 AN: 53216

Other (OTH) AF: 0.00325 AC: 5 AN: 1539

Alfa AF: 0.00308 Hom.: 15

Bravo AF: 0.00698

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0188 AC: 72

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.00176 AC: 214

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Inborn genetic diseases (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	18
DANN	Benign	0.67
DEOGEN2	Benign	0.051	T
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.67	N
PhyloP100		1.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.076
Sift	Benign	0.98	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.19
MVP		0.15
MPC		0.72
ClinPred		0.0030	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.49
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs78979358; hg19: chrX-48337450;