dbSNP rs5744455: TMCO6:c.-129-7943G>A (chr5-140633722-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_011537665.3(TMCO6):c.-129-7943G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 151,962 control chromosomes in the GnomAD database, including 3,374 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 3358 hom., cov: 31)

Exomes 𝑓: 0.16 ( 16 hom. )

Consequence

TMCO6
XM_011537665.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0480

Publications

47 publications found

Variant links:

Genes affected

TMCO6 (HGNC:28814): (transmembrane and coiled-coil domains 6) Predicted to enable nuclear import signal receptor activity. Predicted to be involved in protein import into nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMCO6 links:

CD14 (HGNC:1628): (CD14 molecule) The protein encoded by this gene is a surface antigen that is preferentially expressed on monocytes/macrophages. It cooperates with other proteins to mediate the innate immune response to bacterial lipopolysaccharide, and to viruses. This gene has been identified as a target candidate in the treatment of SARS-CoV-2-infected patients to potentially lessen or inhibit a severe inflammatory response. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2020]

CD14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
TMCO6	XM_011537665.3 link	c.-129-7943G>A	intron_variant	Intron 1 of 10	XP_011535967.1
TMCO6	XM_047417355.1 link	c.-242-6017G>A	intron_variant	Intron 1 of 11	XP_047273311.1
TMCO6	XM_047417356.1 link	c.-255-6017G>A	intron_variant	Intron 1 of 11	XP_047273312.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein
CD14	ENST00000498971.7 link	c.-313C>T	upstream_gene_variant	2	ENSP00000426543.2
CD14	ENST00000512545.2 link	c.-413C>T	upstream_gene_variant	3	ENSP00000425447.2
CD14	ENST00000519715.2 link	c.-292C>T	upstream_gene_variant	4	ENSP00000430884.2

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29277

AN:

151264

Hom.:

3345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0819

Gnomad AMI

AF:

0.0540

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.125

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.163

AC:

AN:

594

Hom.:

Cov.:

AF XY:

0.139

AC XY:

AN XY:

280

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.128

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.214

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.172

AC:

AN:

402

Other (OTH)

AF:

0.105

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.194

AC:

29298

AN:

151368

Hom.:

3358

Cov.:

AF XY:

0.196

AC XY:

14462

AN XY:

73900

show subpopulations

African (AFR)

AF:

0.0816

AC:

3369

AN:

41270

American (AMR)

AF:

0.216

AC:

3280

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

700

AN:

3468

East Asian (EAS)

AF:

0.296

AC:

1523

AN:

5150

South Asian (SAS)

AF:

0.257

AC:

1230

AN:

4792

European-Finnish (FIN)

AF:

0.285

AC:

2943

AN:

10334

Middle Eastern (MID)

AF:

0.115

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.232

AC:

15759

AN:

67852

Other (OTH)

AF:

0.196

AC:

412

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1139

2278

3418

4557

5696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.213

Hom.:

8264

Bravo

AF:

0.181

Asia WGS

AF:

0.312

AC:

1085

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.8

(source)

DANN

Benign

0.69

PhyloP100

0.048

PromoterAI

-0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over