rs2495797

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-54091307-C-A
• chrX-54091307-C-G
• chrX-54091307-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 931516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017848.6. 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
	FAM120C	NM_017848.6	MANE Select	c.2427+5G>T		splice_region intron	N/A	NP_060318.4
	FAM120C	NM_001300788.2		c.2427+5G>T		splice_region intron	N/A	NP_001287717.1	F8W881

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120C	ENST00000375180.7	TSL:1 MANE Select	c.2427+5G>T		splice_region intron	N/A	ENSP00000364324.2	Q9NX05-1
	FAM120C	ENST00000328235.4	TSL:1	c.2427+5G>T		splice_region intron	N/A	ENSP00000329896.4	F8W881

Frequencies

GnomAD3 genomes AF: 0.996 AC: 110456 AN: 110941 Hom.: 38568 Cov.: 23

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

GnomAD2 exomes AF: 0.999 AC: 179200 AN: 179444 AF XY: 0.999

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 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

African (AFR) AF: 0.984 AC: 25487 AN: 25897

American (AMR) AF: 0.999 AC: 34845 AN: 34876

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 19140 AN: 19140

East Asian (EAS) AF: 1.00 AC: 30080 AN: 30080

South Asian (SAS) AF: 1.00 AC: 53033 AN: 53036

European-Finnish (FIN) AF: 1.00 AC: 40482 AN: 40482

Middle Eastern (MID) AF: 0.999 AC: 4042 AN: 4047

European-Non Finnish (NFE) AF: 1.00 AC: 817530 AN: 817569

Other (OTH) AF: 0.999 AC: 45144 AN: 45180

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

African (AFR) AF: 0.985 AC: 30122 AN: 30584

American (AMR) AF: 0.999 AC: 10359 AN: 10373

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2643 AN: 2643

East Asian (EAS) AF: 1.00 AC: 3522 AN: 3522

South Asian (SAS) AF: 1.00 AC: 2614 AN: 2614

European-Finnish (FIN) AF: 1.00 AC: 5824 AN: 5824

Middle Eastern (MID) AF: 1.00 AC: 217 AN: 217

European-Non Finnish (NFE) AF: 1.00 AC: 53019 AN: 53022

Other (OTH) AF: 0.995 AC: 1504 AN: 1511

Alfa AF: 0.998 Hom.: 54341

Bravo AF: 0.995

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.78
PhyloP100		-0.72
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2495797; hg19: chrX-54117740;