chr2-46618834-C-G

Variant names:

• chr2-46618834-C-G
• NM_014171.6:c.78C>G
• CRIPT p.Thr26Thr

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_014171.6(CRIPT):​c.78C>G​(p.Thr26Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T26T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRIPT NM_014171.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 0 publications found

Genes affected

CRIPT (HGNC:14312): (CXXC repeat containing interactor of PDZ3 domain) This gene encodes a protein that binds to the PDZ3 peptide recognition domain. The encoded protein may modulates protein interactions with the cytoskeleton. A mutation in this gene resulted in short stature with microcephaly and distinctive facies. [provided by RefSeq, Jun 2014]

CRIPT Gene-Disease associations (from GenCC):

• Rothmund-Thomson syndrome type 3

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=-0.036 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014171.6. 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
	CRIPT	NM_014171.6	MANE Select	c.78C>G	p.Thr26Thr	synonymous	Exon 2 of 5	NP_054890.1	Q9P021

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRIPT	ENST00000238892.4	TSL:1 MANE Select	c.78C>G	p.Thr26Thr	synonymous	Exon 2 of 5	ENSP00000238892.3	Q9P021
	CRIPT	ENST00000923190.1		c.78C>G	p.Thr26Thr	synonymous	Exon 3 of 6	ENSP00000593249.1
	CRIPT	ENST00000486447.1	TSL:5	n.670C>G		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.9
DANN	Benign	0.78
PhyloP100		-0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-46845973;