dbSNP rs1172113: TMCC2:c.748-11790T>C (chr1-205257160-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_014858.4(TMCC2):c.748-11790T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,232,424 control chromosomes in the GnomAD database, including 93,492 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 0.32 ( 8605 hom., cov: 32)

Exomes 𝑓: 0.39 ( 84887 hom. )

Consequence

TMCC2
NM_014858.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.456

Publications

9 publications found

Variant links:

Genes affected

TMCC2 (HGNC:24239): (transmembrane and coiled-coil domain family 2) Involved in amyloid precursor protein metabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMCC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMCC2	NM_014858.4 link	c.748-11790T>C		intron_variant	Intron 2 of 4	ENST00000358024.8	NP_055673.2	O75069-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMCC2	ENST00000358024.8 link	c.748-11790T>C		intron_variant	Intron 2 of 4	1	NM_014858.4	ENSP00000350718.3		O75069-1

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47976

AN:

151936

Hom.:

8606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.335

GnomAD4 exome

AF:

0.390

AC:

421496

AN:

1080370

Hom.:

84887

Cov.:

AF XY:

0.390

AC XY:

199043

AN XY:

510128

show subpopulations

African (AFR)

AF:

0.188

AC:

4312

AN:

22972

American (AMR)

AF:

0.253

AC:

2158

AN:

8516

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

5380

AN:

14394

East Asian (EAS)

AF:

0.118

AC:

3129

AN:

26530

South Asian (SAS)

AF:

0.154

AC:

3014

AN:

19512

European-Finnish (FIN)

AF:

0.449

AC:

9667

AN:

21524

Middle Eastern (MID)

AF:

0.283

AC:

827

AN:

2918

European-Non Finnish (NFE)

AF:

0.411

AC:

378116

AN:

920312

Other (OTH)

AF:

0.341

AC:

14893

AN:

43692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

14774

29548

44323

59097

73871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13332

26664

39996

53328

66660

<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:

0.316

AC:

47984

AN:

152054

Hom.:

8605

Cov.:

AF XY:

0.313

AC XY:

23279

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.188

AC:

7807

AN:

41498

American (AMR)

AF:

0.274

AC:

4187

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1269

AN:

3470

East Asian (EAS)

AF:

0.105

AC:

544

AN:

5158

South Asian (SAS)

AF:

0.155

AC:

746

AN:

4818

European-Finnish (FIN)

AF:

0.461

AC:

4871

AN:

10576

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.405

AC:

27532

AN:

67924

Other (OTH)

AF:

0.330

AC:

698

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1626

3252

4878

6504

8130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.369

Hom.:

1338

Bravo

AF:

0.296

Asia WGS

AF:

0.135

AC:

475

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.46

PromoterAI

-0.0050

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over