10-131116863-G-C

Variant names:

• chr10-131116863-G-C
• rs199911619
• NM_174937.4:c.1331C>G

Variant summary

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

The NM_174937.4(TCERG1L):​c.1331C>G​(p.Pro444Arg) 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. 14/22 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. P444L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCERG1L NM_174937.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 0 publications found

Genes affected

TCERG1L (HGNC:23533): (transcription elongation regulator 1 like) Predicted to enable RNA polymerase binding activity and transcription coregulator activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.21141079).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174937.4. 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
	TCERG1L	NM_174937.4	MANE Select	c.1331C>G	p.Pro444Arg	missense	Exon 9 of 12	NP_777597.2	Q5VWI1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCERG1L	ENST00000368642.4	TSL:1 MANE Select	c.1331C>G	p.Pro444Arg	missense	Exon 9 of 12	ENSP00000357631.4	Q5VWI1
	TCERG1L	ENST00000935680.1		c.1370C>G	p.Pro457Arg	missense	Exon 10 of 13	ENSP00000605739.1
	TCERG1L	ENST00000483040.1	TSL:5	n.3193C>G		non_coding_transcript_exon	Exon 9 of 12

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.1
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.083
Sift	Benign	0.13	T
Sift4G	Benign	0.28	T
Polyphen		0.96	D
Vest4		0.42
MutPred		0.25		Loss of glycosylation at T441 (P = 0.0254)
MVP		0.49
MPC		0.13
ClinPred		0.66	D
GERP RS		4.2
Varity_R		0.091
gMVP		0.37
Mutation Taster		=88/12	polymorphism

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: rs199911619; hg19: chr10-132915126;