17-30803948-T-A

Variant names:

• chr17-30803948-T-A
• NM_015986.4:c.290A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015986.4(CRLF3):​c.290A>T​(p.Lys97Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRLF3 NM_015986.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04

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]

ENSG00000276250 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4159619).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRLF3	NM_015986.4	c.290A>T	p.Lys97Met	missense_variant	Exon 2 of 8	ENST00000324238.7	NP_057070.3
CRLF3	NR_073118.2	n.171-6550A>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRLF3	ENST00000324238.7	c.290A>T	p.Lys97Met	missense_variant	Exon 2 of 8	1	NM_015986.4	ENSP00000318804.6
CRLF3	ENST00000583805.1	n.573A>T		non_coding_transcript_exon_variant	Exon 2 of 2	4
ENSG00000276250	ENST00000621598.1	n.295T>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
CRLF3	ENST00000578692.1	n.130-6550A>T		intron_variant	Intron 1 of 6	2		ENSP00000462643.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290A>T (p.K97M) alteration is located in exon 2 (coding exon 2) of the CRLF3 gene. This alteration results from a A to T substitution at nucleotide position 290, causing the lysine (K) at amino acid position 97 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.12
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.50
MutPred		0.33		Loss of methylation at K97 (P = 0.0175);
MVP		0.25
MPC		1.2
ClinPred		0.94	D
GERP RS		4.9
Varity_R		0.22
gMVP		0.52

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: chr17-29130966;