Variant 17-74795600-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000335464.10(TMEM104):c.604C>G(p.Leu202Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00482 in 1,614,002 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 32 hom. )

Consequence

TMEM104
ENST00000335464.10 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

TMEM104 (HGNC:25984): (transmembrane protein 104) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM104 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007980257).

BP6

Variant 17-74795600-C-G is Benign according to our data. Variant chr17-74795600-C-G is described in ClinVar as [Benign]. Clinvar id is 782159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM104	NM_017728.4 linkuse as main transcript	c.604C>G	p.Leu202Val	missense_variant	8/10	ENST00000335464.10	NP_060198.3	Q8NE00-1A0A024R8L3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM104	ENST00000335464.10 linkuse as main transcript	c.604C>G	p.Leu202Val	missense_variant	8/10	1	NM_017728.4	ENSP00000334849.5		Q8NE00-1

Frequencies

GnomAD3 genomes

AF:

0.00527

AC:

802

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00457

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00541

AC:

1358

AN:

250988

Hom.:

AF XY:

0.00504

AC XY:

684

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.000679

Gnomad AMR exome

AF:

0.00738

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.0199

Gnomad NFE exome

AF:

0.00517

Gnomad OTH exome

AF:

0.00604

GnomAD4 exome

AF:

0.00478

AC:

6984

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

3426

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00738

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.0207

Gnomad4 NFE exome

AF:

0.00461

Gnomad4 OTH exome

AF:

0.00485

GnomAD4 genome

AF:

0.00526

AC:

801

AN:

152252

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

449

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.0200

Gnomad4 NFE

AF:

0.00457

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.00461

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00495

AC:

601

EpiCase

AF:

0.00393

EpiControl

AF:

0.00439

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 28, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0092

T;T;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.86

D;D;D;.

MetaRNN

Benign

0.0080

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.060

N;.;N;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.38

N;N;.;.

REVEL

Benign

0.073

Sift

Benign

0.43

T;.;.;.

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.33

MVP

0.25

MPC

0.22

ClinPred

0.013

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.75

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

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