chrX-54091307-C-G

Variant names:

• chrX-54091307-C-G
• rs2495797
• NM_017848.6:c.2427+5G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017848.6(FAM120C):​c.2427+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: FAM120C NM_017848.6 splice_region, intron
• Scores: Splicing: ADA: 0.8889
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120C	NM_017848.6	c.2427+5G>C		splice_region_variant, intron_variant	Intron 11 of 15	ENST00000375180.7	NP_060318.4
FAM120C	NM_001300788.2	c.2427+5G>C		splice_region_variant, intron_variant	Intron 11 of 13		NP_001287717.1
FAM120C	XM_006724589.5	c.2427+5G>C		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	c.2427+5G>C		splice_region_variant, intron_variant	Intron 11 of 15	1	NM_017848.6	ENSP00000364324.2
FAM120C	ENST00000328235.4	c.2427+5G>C		splice_region_variant, intron_variant	Intron 11 of 13	1		ENSP00000329896.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1070309 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 340437

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.89
dbscSNV1_RF	Benign	0.59
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

Publications

LitVar

Other links and lift over

dbSNP: rs2495797; hg19: chrX-54117740;