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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014858.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMCC2	NM_014858.4	MANE Select	c.748-11790T>C	intron	N/A	NP_055673.2	O75069-1
TMCC2	NM_001242925.2		c.514-11790T>C	intron	N/A	NP_001229854.1	O75069-2
TMCC2	NM_001375651.1		c.514-11790T>C	intron	N/A	NP_001362580.1	O75069-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TMCC2	ENST00000358024.8	TSL:1 MANE Select	c.748-11790T>C	intron	N/A	ENSP00000350718.3	O75069-1
TMCC2	ENST00000637895.1	TSL:1	c.72+10469T>C	intron	N/A	ENSP00000490308.1	O75069-5
TMCC2	ENST00000481950.2	TSL:1	n.72+10469T>C	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over