Variant 17-74790238-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_017728.4(TMEM104):c.288C>T(p.Ser96=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,614,040 control chromosomes in the GnomAD database, including 196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 15 hom., cov: 30)

Exomes 𝑓: 0.015 ( 181 hom. )

Consequence

TMEM104
NM_017728.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.450

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 17-74790238-C-T is Benign according to our data. Variant chr17-74790238-C-T is described in ClinVar as [Benign]. Clinvar id is 773593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.45 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0108 (1638/152298) while in subpopulation NFE AF= 0.0169 (1149/68012). AF 95% confidence interval is 0.0161. There are 15 homozygotes in gnomad4. There are 777 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM104	NM_017728.4 linkuse as main transcript	c.288C>T	p.Ser96=	synonymous_variant	5/10	ENST00000335464.10	NP_060198.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM104	ENST00000335464.10 linkuse as main transcript	c.288C>T	p.Ser96=	synonymous_variant	5/10	1	NM_017728.4	ENSP00000334849	P1	Q8NE00-1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1638

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.0108

AC:

2706

AN:

251438

Hom.:

AF XY:

0.0108

AC XY:

1464

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00899

Gnomad ASJ exome

AF:

0.00804

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.0150

AC:

21888

AN:

1461742

Hom.:

181

Cov.:

AF XY:

0.0145

AC XY:

10561

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.00890

Gnomad4 ASJ exome

AF:

0.00746

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.00939

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.0108

AC:

1638

AN:

152298

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

777

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.0169

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0153

EpiControl

AF:

0.0139

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	Sep 28, 2017	- -
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

-0.25

CADD

Benign

5.7

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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