Variant chr17-44014899-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032376.4(TMEM101):c.54G>A(p.Leu18Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,614,028 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 16 hom., cov: 33)

Exomes 𝑓: 0.0083 ( 72 hom. )

Consequence

TMEM101
NM_032376.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

TMEM101 (HGNC:28653): (transmembrane protein 101) Involved in positive regulation of I-kappaB kinase/NF-kappaB signaling. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM101 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 17-44014899-C-T is Benign according to our data. Variant chr17-44014899-C-T is described in ClinVar as [Benign]. Clinvar id is 774518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1850/152378) while in subpopulation AFR AF= 0.0279 (1160/41582). AF 95% confidence interval is 0.0266. There are 16 homozygotes in gnomad4. There are 885 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM101	NM_032376.4 linkuse as main transcript	c.54G>A	p.Leu18Leu	synonymous_variant	1/4	ENST00000206380.8	NP_115752.1	Q96IK0
TMEM101	NM_001304813.2 linkuse as main transcript	c.-38+85G>A		intron_variant			NP_001291742.1	Q96IK0B4DFS4
TMEM101	NM_001304814.2 linkuse as main transcript	c.-38+85G>A		intron_variant			NP_001291743.1	Q96IK0B4DFS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM101	ENST00000206380.8 linkuse as main transcript	c.54G>A	p.Leu18Leu	synonymous_variant	1/4	1	NM_032376.4	ENSP00000206380.3		Q96IK0

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1846

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0279

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00896

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00769

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00602

AC:

1512

AN:

251160

Hom.:

AF XY:

0.00528

AC XY:

717

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0267

Gnomad AMR exome

AF:

0.00617

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00711

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00829

AC:

12116

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00779

AC XY:

5661

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0302

Gnomad4 AMR exome

AF:

0.00640

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00911

Gnomad4 OTH exome

AF:

0.00982

GnomAD4 genome

AF:

0.0121

AC:

1850

AN:

152378

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

885

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0279

Gnomad4 AMR

AF:

0.00895

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00769

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.00824

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over