19-18588898-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001100418.2(REX1BD):c.97T>G(p.Trp33Gly) variant causes a missense, splice region 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. 12/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: REX1BD NM_001100418.2 missense, splice_region
• Scores: Splicing: ADA: 0.003306
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.634

Genes affected

REX1BD (HGNC:26098): (required for excision 1-B domain containing)

CRLF1 (HGNC:2364): (cytokine receptor like factor 1) This gene encodes a member of the cytokine type I receptor family. The protein forms a secreted complex with cardiotrophin-like cytokine factor 1 and acts on cells expressing ciliary neurotrophic factor receptors. The complex can promote survival of neuronal cells. Mutations in this gene result in Crisponi syndrome and cold-induced sweating syndrome. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1920709).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REX1BD	NM_001100418.2	c.97T>G	p.Trp33Gly	missense_variant, splice_region_variant	1/5	ENST00000358607.11
REX1BD	NM_001100419.2	c.97T>G	p.Trp33Gly	missense_variant, splice_region_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REX1BD	ENST00000358607.11	c.97T>G	p.Trp33Gly	missense_variant, splice_region_variant	1/5	1	NM_001100418.2

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.97T>G (p.W33G) alteration is located in exon 1 (coding exon 1) of the C19orf60 gene. This alteration results from a T to G substitution at nucleotide position 97, causing the tryptophan (W) at amino acid position 33 to be replaced by a glycine (G). 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	Uncertain	0.39
BayesDel_addAF	Benign	0.0049	T
BayesDel_noAF	Benign	-0.23
Cadd	Pathogenic	26
Dann	Benign	0.94
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	0.065
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.52	T
MutationTaster	Benign	0.64	D;D
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;.
Vest4		0.26
MutPred		0.42		Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP		0.29
MPC		1.7
ClinPred		0.86	D
GERP RS		2.5
Varity_R		0.39
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0033
dbscSNV1_RF	Benign	0.080
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: chr19-18699708;