Genetic Variant FAM120C:c.2427+5G>T (chrX-54091307-C-A) – ACMG Classification: Benign (-12 pts)

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

Splicing: ADA: 0.9199

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]

FAM120C links:

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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	Effect	Exon rank	MANE	Protein	UniProt
FAM120C	NM_017848.6 link	c.2427+5G>T	splice_region_variant, intron_variant	Intron 11 of 15	ENST00000375180.7	NP_060318.4	Q9NX05-1
FAM120C	NM_001300788.2 link	c.2427+5G>T	splice_region_variant, intron_variant	Intron 11 of 13		NP_001287717.1	F8W881
FAM120C	XM_006724589.5 link	c.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
FAM120C	ENST00000375180.7 link	c.2427+5G>T		splice_region_variant, intron_variant	Intron 11 of 15	1	NM_017848.6	ENSP00000364324.2		Q9NX05-1
FAM120C	ENST00000328235.4 link	c.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.:

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.:

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.:

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

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.

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