X-54091307-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_017848.6(FAM120C):​c.2427+5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 38563 hom., 33028 hem., cov: 23)
Exomes 𝑓: 1.0 ( 364547 hom. 340302 hem. )
Failed GnomAD Quality Control

Consequence

FAM120C
NM_017848.6 splice_region, intron

Scores

2
Splicing: ADA: 0.9199
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.723
Variant links:
Genes affected
FAM120C (HGNC:16949): (family with sequence similarity 120 member C) This gene encodes a potential transmembrane protein and lies in a region where mutations and deletions have been associated with intellectual disability and autism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant X-54091307-C-A is Benign according to our data. Variant chrX-54091307-C-A is described in ClinVar as [Benign]. Clinvar id is 931516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM120CNM_017848.6 linkc.2427+5G>T splice_region_variant, intron_variant Intron 11 of 15 ENST00000375180.7 NP_060318.4 Q9NX05-1
FAM120CNM_001300788.2 linkc.2427+5G>T splice_region_variant, intron_variant Intron 11 of 13 NP_001287717.1 F8W881
FAM120CXM_006724589.5 linkc.2427+5G>T splice_region_variant, intron_variant Intron 11 of 14 XP_006724652.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM120CENST00000375180.7 linkc.2427+5G>T splice_region_variant, intron_variant Intron 11 of 15 1 NM_017848.6 ENSP00000364324.2 Q9NX05-1
FAM120CENST00000328235.4 linkc.2427+5G>T splice_region_variant, intron_variant Intron 11 of 13 1 ENSP00000329896.4 F8W881

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
110456
AN:
110941
Hom.:
38568
Cov.:
23
AF XY:
0.996
AC XY:
32970
AN XY:
33097
FAILED QC
Gnomad AFR
AF:
0.985
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.999
Gnomad ASJ
AF:
1.00
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
1.00
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
1.00
Gnomad NFE
AF:
1.00
Gnomad OTH
AF:
0.995
GnomAD3 exomes
AF:
0.999
AC:
179200
AN:
179444
Hom.:
57443
AF XY:
0.999
AC XY:
64113
AN XY:
64156
show subpopulations
Gnomad AFR exome
AF:
0.984
Gnomad AMR exome
AF:
0.999
Gnomad ASJ exome
AF:
1.00
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
1.00
Gnomad FIN exome
AF:
1.00
Gnomad NFE exome
AF:
1.00
Gnomad OTH exome
AF:
1.00
GnomAD4 exome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
1.00
AC:
1069783
AN:
1070307
Hom.:
364547
Cov.:
20
AF XY:
1.00
AC XY:
340302
AN XY:
340437
show subpopulations
Gnomad4 AFR exome
AF:
0.984
Gnomad4 AMR exome
AF:
0.999
Gnomad4 ASJ exome
AF:
1.00
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
1.00
Gnomad4 FIN exome
AF:
1.00
Gnomad4 NFE exome
AF:
1.00
Gnomad4 OTH exome
AF:
0.999
GnomAD4 genome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.996
AC:
110504
AN:
110990
Hom.:
38563
Cov.:
23
AF XY:
0.996
AC XY:
33028
AN XY:
33156
show subpopulations
Gnomad4 AFR
AF:
0.985
Gnomad4 AMR
AF:
0.999
Gnomad4 ASJ
AF:
1.00
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
1.00
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
1.00
Gnomad4 OTH
AF:
0.995
Alfa
AF:
0.999
Hom.:
32923
Bravo
AF:
0.995

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Nov 11, 2019
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. This variant was detected in hemizygous state. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
CADD
Benign
17
DANN
Benign
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.92
dbscSNV1_RF
Benign
0.64
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs2495797; hg19: chrX-54117740; API