CDK5RAP1 p.Gln346His

Variant names:

• chr20-33379530-C-A
• NM_016408.4:c.1038G>T
• CDK5RAP1 p.Gln346His

Your query was ambiguous. Multiple possible variants found:

• chr20-33379530-C-A
• chr20-33379530-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016408.4(CDK5RAP1):​c.1038G>T​(p.Gln346His) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q346R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK5RAP1 NM_016408.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 0 publications found

Genes affected

CDK5RAP1 (HGNC:15880): (CDK5 regulatory subunit associated protein 1) This gene encodes a regulator of cyclin-dependent kinase 5 activity. This protein has also been reported to modify RNA by adding a methylthio-group and may thus have a dual function as an RNA methylthiotransferase and as an inhibitor of cyclin-dependent kinase 5 activity. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14415291).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016408.4. 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
	CDK5RAP1	NM_016408.4	MANE Select	c.1038G>T	p.Gln346His	missense	Exon 8 of 14	NP_057492.2
	CDK5RAP1	NM_001365728.1		c.1080G>T	p.Gln360His	missense	Exon 9 of 15	NP_001352657.1	Q96SZ6-1
	CDK5RAP1	NM_016082.4		c.1041G>T	p.Gln347His	missense	Exon 8 of 14	NP_057166.4	Q96SZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK5RAP1	ENST00000346416.7	TSL:1 MANE Select	c.1038G>T	p.Gln346His	missense	Exon 8 of 14	ENSP00000217372.2	Q96SZ6-3
	CDK5RAP1	ENST00000339269.5	TSL:1	c.877-5318G>T		intron	N/A	ENSP00000341840.5	Q96SZ6-4
	CDK5RAP1	ENST00000874266.1		c.1131G>T	p.Gln377His	missense	Exon 9 of 15	ENSP00000544325.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.27
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.19
Sift	Benign	0.10	T
Sift4G	Benign	0.12	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.056
gMVP		0.57
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-31967336;