3-108162602-C-G

Variant names:

• chr3-108162602-C-G
• NM_018010.4:c.1165G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_018010.4(IFT57):​c.1165G>C​(p.Glu389Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFT57 NM_018010.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.38

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]

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 (MetaRNN=0.085933805).
• BP6: Variant 3-108162602-C-G is Benign according to our data. Variant chr3-108162602-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3527929.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT57	NM_018010.4	c.1165G>C	p.Glu389Gln	missense_variant	Exon 11 of 11	ENST00000264538.4	NP_060480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT57	ENST00000264538.4	c.1165G>C	p.Glu389Gln	missense_variant	Exon 11 of 11	1	NM_018010.4	ENSP00000264538.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 11, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.13
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.98	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.21
Sift	Benign	0.82	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.097
MutPred		0.36		Gain of MoRF binding (P = 0.0266);
MVP		0.30
MPC		0.20
ClinPred		0.39	T
GERP RS		5.0
Varity_R		0.12
gMVP		0.097

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-107881449;