Genetic Variant NM_198584.3:c.456T>C (chr8-85267907-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_198584.3(CA13):c.456T>C(p.Gly152Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00769 in 1,593,808 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 57 hom. )

Consequence

CA13
NM_198584.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.545

Publications

1 publications found

Variant links:

Genes affected

CA13 (HGNC:14914): (carbonic anhydrase 13) Predicted to enable carbonate dehydratase activity. Predicted to be involved in one-carbon metabolic process. Predicted to be located in intracellular membrane-bounded organelle and myelin sheath. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CA13 links:

ENSG00000300073 (HGNC:):

ENSG00000300073 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 8-85267907-T-C is Benign according to our data. Variant chr8-85267907-T-C is described in ClinVar as Benign. ClinVar VariationId is 713332.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.545 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198584.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA13	NM_198584.3	MANE Select	c.456T>C	p.Gly152Gly	synonymous	Exon 5 of 7	NP_940986.1	Q8N1Q1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CA13	ENST00000321764.4	TSL:1 MANE Select	c.456T>C	p.Gly152Gly	synonymous	Exon 5 of 7	ENSP00000318912.3	Q8N1Q1
CA13	ENST00000517298.5	TSL:5	n.1187T>C		non_coding_transcript_exon	Exon 7 of 8
ENSG00000300073	ENST00000768675.1		n.248-534A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00545

AC:

829

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00414

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00861

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00553

AC:

1359

AN:

245662

AF XY:

0.00542

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00770

Gnomad ASJ exome

AF:

0.00285

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00522

Gnomad NFE exome

AF:

0.00792

Gnomad OTH exome

AF:

0.00719

GnomAD4 exome

AF:

0.00793

AC:

11430

AN:

1441458

Hom.:

Cov.:

AF XY:

0.00752

AC XY:

5398

AN XY:

717642

show subpopulations

African (AFR)

AF:

0.00130

AC:

AN:

33004

American (AMR)

AF:

0.00786

AC:

345

AN:

43902

Ashkenazi Jewish (ASJ)

AF:

0.00206

AC:

AN:

25764

East Asian (EAS)

AF:

0.00

AC:

AN:

39450

South Asian (SAS)

AF:

0.000296

AC:

AN:

84382

European-Finnish (FIN)

AF:

0.00508

AC:

270

AN:

53158

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.00935

AC:

10246

AN:

1096370

Other (OTH)

AF:

0.00737

AC:

440

AN:

59710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

455

910

1366

1821

2276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.00544

AC:

829

AN:

152350

Hom.:

Cov.:

AF XY:

0.00507

AC XY:

378

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00127

AC:

AN:

41586

American (AMR)

AF:

0.00830

AC:

127

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00414

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00861

AC:

586

AN:

68030

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.00604

Asia WGS

AF:

0.000289

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.4

(source)

DANN

Benign

0.73

PhyloP100

0.55

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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