17-30792477-C-T

Variant names:

• chr17-30792477-C-T
• rs751773627
• NM_015986.4:c.922G>A

Variant summary

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

The NM_015986.4(CRLF3):​c.922G>A​(p.Ala308Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A308S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
• Consequence: CRLF3 NM_015986.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55
• Publications: 0 publications found

Genes affected

CRLF3 (HGNC:17177): (cytokine receptor like factor 3) This gene encodes a cytokine receptor-like factor that may negatively regulate cell cycle progression at the G0/G1 phase. Studies of the related rat protein suggest that it may regulate neuronal morphology and synaptic vesicle biogenesis. This gene is one of several genes located in the neurofibromatosis type I tumor suppressor region on the q arm of chromosome 17, a region that is subject to microdeletions, duplications, chromosomal breaks and rearrangements. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2 and 5. [provided by RefSeq, Aug 2012]

ENSG00000290928 (HGNC:):

SUZ12P1 (HGNC:32421): (SUZ12 pseudogene 1)

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=0.13872054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015986.4. 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
	CRLF3	NM_015986.4	MANE Select	c.922G>A	p.Ala308Thr	missense	Exon 6 of 8	NP_057070.3
	CRLF3	NR_073118.2		n.755G>A		non_coding_transcript_exon	Exon 5 of 7
	SUZ12P1	NR_144394.1		n.2906C>T		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRLF3	ENST00000324238.7	TSL:1 MANE Select	c.922G>A	p.Ala308Thr	missense	Exon 6 of 8	ENSP00000318804.6	Q8IUI8-1
	CRLF3	ENST00000921129.1		c.943G>A	p.Ala315Thr	missense	Exon 6 of 8	ENSP00000591188.1
	CRLF3	ENST00000885412.1		c.922G>A	p.Ala308Thr	missense	Exon 6 of 8	ENSP00000555471.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74338

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.055
Sift	Benign	0.46	T
Sift4G	Benign	0.75	T
Polyphen		0.049	B
Vest4		0.19
MutPred		0.21		Gain of phosphorylation at A308 (P = 0.0649)
MVP		0.21
MPC		0.33
ClinPred		0.52	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.46

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

Other links and lift over

dbSNP: rs751773627; hg19: chr17-29119495;