10-131093202-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_174937.4(TCERG1L):c.1721G>A(p.Arg574Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0075 in 1,613,858 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (38 hom.)
• Consequence: TCERG1L NM_174937.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.17

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008210033).
• BP6: Variant 10-131093202-C-T is Benign according to our data. Variant chr10-131093202-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 771744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCERG1L	NM_174937.4	c.1721G>A	p.Arg574Gln	missense_variant	12/12	ENST00000368642.4
TCERG1L	XM_047424966.1	c.1760G>A	p.Arg587Gln	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCERG1L	ENST00000368642.4	c.1721G>A	p.Arg574Gln	missense_variant	12/12	1	NM_174937.4	P1
TCERG1L	ENST00000483040.1	n.3583G>A		non_coding_transcript_exon_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.00550 AC: 836 AN: 152122 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00926

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00575 AC: 1444 AN: 251118 Hom.: 4 AF XY: 0.00607 AC XY: 824 AN XY: 135714

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00454

Gnomad FIN exome AF: 0.00509

Gnomad NFE exome AF: 0.00888

Gnomad OTH exome AF: 0.00686

GnomAD4 exome AF: 0.00771 AC: 11264 AN: 1461618 Hom.: 38 Cov.: 31 AF XY: 0.00769 AC XY: 5589 AN XY: 727096

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.00340

Gnomad4 ASJ exome AF: 0.00184

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00449

Gnomad4 FIN exome AF: 0.00506

Gnomad4 NFE exome AF: 0.00887

Gnomad4 OTH exome AF: 0.00835

GnomAD4 genome AF: 0.00547 AC: 833 AN: 152240 Hom.: 10 Cov.: 32 AF XY: 0.00517 AC XY: 385 AN XY: 74412

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.00926

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00692 Hom.: 9

Bravo AF: 0.00509

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.00804 AC: 31

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00942 AC: 81

ExAC AF: 0.00563 AC: 684

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00769

EpiControl AF: 0.00747

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
Cadd	Pathogenic	28
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.010	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.0082	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.24
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.65
MVP		0.70
MPC		0.49
ClinPred		0.019	T
GERP RS		4.9
Varity_R		0.34
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs139123582; hg19: chr10-132891465;