Genetic Variant NM_174937.4:c.1322C>T (chr10-131116872-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_174937.4(TCERG1L):c.1322C>T(p.Thr441Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000883 in 1,596,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

TCERG1L
NM_174937.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Publications

0 publications found

Variant links:

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]

TCERG1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018124282).

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.1322C>T	p.Thr441Met	missense	Exon 9 of 12	NP_777597.2	Q5VWI1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCERG1L	ENST00000368642.4	TSL:1 MANE Select	c.1322C>T	p.Thr441Met	missense	Exon 9 of 12	ENSP00000357631.4	Q5VWI1
TCERG1L	ENST00000935680.1		c.1361C>T	p.Thr454Met	missense	Exon 10 of 13	ENSP00000605739.1
TCERG1L	ENST00000483040.1	TSL:5	n.3184C>T		non_coding_transcript_exon	Exon 9 of 12

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000144

AC:

AN:

221952

AF XY:

0.000134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00253

Gnomad EAS exome

AF:

0.000123

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000606

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000838

AC:

121

AN:

1443782

Hom.:

Cov.:

AF XY:

0.0000838

AC XY:

AN XY:

716276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33162

American (AMR)

AF:

0.00

AC:

AN:

42088

Ashkenazi Jewish (ASJ)

AF:

0.00263

AC:

AN:

25818

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38850

South Asian (SAS)

AF:

0.0000241

AC:

AN:

82990

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000362

AC:

AN:

1103916

Other (OTH)

AF:

0.000167

AC:

AN:

59794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000131

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.000388

AC:

AN:

5152

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000124

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.66

M_CAP

Benign

0.0047

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

3.3

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.069

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.050

Polyphen

0.90

Vest4

0.39

MVP

0.50

MPC

0.45

ClinPred

0.15

GERP RS

4.2

Varity_R

0.069

gMVP

0.46

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over