3-108162661-G-C

Variant names:

• chr3-108162661-G-C
• rs1421881056
• NM_018010.4:c.1112-6C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018010.4(IFT57):​c.1112-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,510 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IFT57 NM_018010.4 splice_region, intron
• Scores: Splicing: ADA: 0.001391
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483
• Publications: 0 publications found

Genes affected

IFT57 (HGNC:17367): (intraflagellar transport 57) Predicted to enable DNA binding activity. Acts upstream of or within activation of cysteine-type endopeptidase activity involved in apoptotic process; apoptotic process; and regulation of apoptotic process. Predicted to be located in ciliary basal body. Predicted to be part of axoneme and intraciliary transport particle B. Predicted to be active in Golgi apparatus; centrosome; and cilium. Implicated in orofaciodigital syndrome. [provided by Alliance of Genome Resources, Apr 2022]

IFT57 Gene-Disease associations (from GenCC):

• orofaciodigital syndrome 18

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018010.4. 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
	IFT57	NM_018010.4	MANE Select	c.1112-6C>G		splice_region intron	N/A	NP_060480.1	Q9NWB7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT57	ENST00000264538.4	TSL:1 MANE Select	c.1112-6C>G		splice_region intron	N/A	ENSP00000264538.3	Q9NWB7
	IFT57	ENST00000878338.1		c.1223-6C>G		splice_region intron	N/A	ENSP00000548397.1
	IFT57	ENST00000939116.1		c.1205-6C>G		splice_region intron	N/A	ENSP00000609175.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000436 AC: 1 AN: 229210 AF XY: 0.00000805

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000955

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425510 Hom.: 0 Cov.: 28 AF XY: 0.00000142 AC XY: 1 AN XY: 706378

African (AFR) AF: 0.00 AC: 0 AN: 32080

American (AMR) AF: 0.00 AC: 0 AN: 40134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24912

East Asian (EAS) AF: 0.00 AC: 0 AN: 38958

South Asian (SAS) AF: 0.00 AC: 0 AN: 81520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090988

Other (OTH) AF: 0.00 AC: 0 AN: 58686

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0014
dbscSNV1_RF	Benign	0.036
SpliceAI score (max)		0.0		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: rs1421881056; hg19: chr3-107881508;