Genetic Variant PCMT1:c.*605A>T (chr6-149811183-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001360452.2(PCMT1):c.*605A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,562 control chromosomes in the GnomAD database, including 24,873 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 0.53 ( 24839 hom., cov: 32)

Exomes 𝑓: 0.34 ( 34 hom. )

Consequence

PCMT1
NM_001360452.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.962

Publications

17 publications found

Variant links:

Genes affected

PCMT1 (HGNC:8728): (protein-L-isoaspartate (D-aspartate) O-methyltransferase) This gene encodes a member of the type II class of protein carboxyl methyltransferase enzymes. The encoded enzyme plays a role in protein repair by recognizing and converting D-aspartyl and L-isoaspartyl residues resulting from spontaneous deamidation back to the normal L-aspartyl form. The encoded protein may play a protective role in the pathogenesis of Alzheimer's disease, and single nucleotide polymorphisms in this gene have been associated with spina bifida and premature ovarian failure. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

PCMT1 links:

ENSG00000285889 (HGNC:):

ENSG00000285889 links:

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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=-0.54).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360452.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PCMT1	NM_001360452.2	MANE Select	c.*605A>T	3_prime_UTR	Exon 8 of 8	NP_001347381.1
PCMT1	NM_001252049.1		c.*555A>T	3_prime_UTR	Exon 8 of 8	NP_001238978.1
PCMT1	NM_005389.2		c.*605A>T	3_prime_UTR	Exon 8 of 8	NP_005380.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PCMT1	ENST00000464889.7	TSL:1 MANE Select	c.*605A>T	3_prime_UTR	Exon 8 of 8	ENSP00000420813.2
PCMT1	ENST00000367384.8	TSL:1	c.*555A>T	3_prime_UTR	Exon 8 of 8	ENSP00000356354.3
PCMT1	ENST00000367380.9	TSL:2	c.*605A>T	3_prime_UTR	Exon 7 of 7	ENSP00000356350.6

Frequencies

GnomAD3 genomes

AF:

0.533

AC:

80982

AN:

151956

Hom.:

24771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.365

Gnomad AMR

AF:

0.603

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.828

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.362

Gnomad OTH

AF:

0.529

GnomAD4 exome

AF:

0.344

AC:

168

AN:

488

Hom.:

Cov.:

AF XY:

0.341

AC XY:

107

AN XY:

314

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.337

AC:

120

AN:

356

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.307

AC:

AN:

114

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.533

AC:

81111

AN:

152074

Hom.:

24839

Cov.:

AF XY:

0.537

AC XY:

39947

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.806

AC:

33435

AN:

41506

American (AMR)

AF:

0.604

AC:

9216

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1562

AN:

3470

East Asian (EAS)

AF:

0.830

AC:

4294

AN:

5176

South Asian (SAS)

AF:

0.505

AC:

2433

AN:

4820

European-Finnish (FIN)

AF:

0.378

AC:

3985

AN:

10552

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.362

AC:

24590

AN:

67968

Other (OTH)

AF:

0.534

AC:

1127

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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

674

1348

2022

2696

3370

<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:

0.244

Hom.:

473

Bravo

AF:

0.568

Asia WGS

AF:

0.666

AC:

2317

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.96

Mutation Taster

=97/3

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over