NM_004918.4:c.371C>G

Variant names:

• chr14-95691305-C-G
• rs755390466
• NM_004918.4:c.371C>G

Variant summary

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

The NM_004918.4(TCL1B):​c.371C>G​(p.Pro124Arg) 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. 13/22 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. P124L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCL1B NM_004918.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 1 publications found

Genes affected

TCL1B (HGNC:11649): (TCL1 family AKT coactivator B) Enables protein kinase binding activity and protein serine/threonine kinase activator activity. Involved in positive regulation of peptidyl-serine phosphorylation and positive regulation of protein serine/threonine kinase activity. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259084 (HGNC:):

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=0.21099347).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004918.4. 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
	TCL1B	NM_004918.4	MANE Select	c.371C>G	p.Pro124Arg	missense	Exon 3 of 4	NP_004909.1	O95988

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCL1B	ENST00000340722.8	TSL:1 MANE Select	c.371C>G	p.Pro124Arg	missense	Exon 3 of 4	ENSP00000343223.6	O95988
	ENSG00000259084	ENST00000461160.5	TSL:1	n.2845C>G		non_coding_transcript_exon	Exon 7 of 8
	TCL1B	ENST00000464815.5	TSL:1	n.401C>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.17
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.12
MutPred		0.60		Loss of glycosylation at P124 (P = 0.0227)
MVP		0.18
MPC		0.87
ClinPred		0.78	D
GERP RS		-2.1
Varity_R		0.56
gMVP		0.091
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs755390466; hg19: chr14-96157642;