dbSNP rs1058511: KMT5C:c.*622C>A (chr19-55348071-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_032701.4(KMT5C):c.*622C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,634 control chromosomes in the GnomAD database, including 16,802 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 0.46 ( 16754 hom., cov: 33)

Exomes 𝑓: 0.42 ( 48 hom. )

Consequence

KMT5C
NM_032701.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.195

Publications

20 publications found

Variant links:

Genes affected

KMT5C (HGNC:28405): (lysine methyltransferase 5C) SUV420H2 and the related enzyme SUV420H1 (MIM 610881) function as histone methyltransferases that specifically trimethylate nucleosomal histone H4 (see MIM 602822) on lysine-20 (K20) (Schotta et al., 2004 [PubMed 15145825]).[supplied by OMIM, Dec 2009]

KMT5C 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=-0.4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMT5C	NM_032701.4 link	c.*622C>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000255613.8	NP_116090.2	Q86Y97-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KMT5C	ENST00000255613.8 link	c.*622C>A	3_prime_UTR_variant	Exon 9 of 9	1	NM_032701.4	ENSP00000255613.3	Q86Y97-1
KMT5C	ENST00000630497.1 link	c.*622C>A	3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000486397.1	A0A0D9SF94
KMT5C	ENST00000445196.5 link	n.*1551C>A	non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000397296.1	Q86Y97-2
KMT5C	ENST00000445196.5 link	n.*1551C>A	3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000397296.1	Q86Y97-2

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70375

AN:

152016

Hom.:

16724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.737

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.414

Gnomad OTH

AF:

0.458

GnomAD4 exome

AF:

0.418

AC:

208

AN:

498

Hom.:

Cov.:

AF XY:

0.429

AC XY:

132

AN XY:

308

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.423

AC:

181

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.320

AC:

AN:

Other (OTH)

AF:

0.583

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.463

AC:

70449

AN:

152136

Hom.:

16754

Cov.:

AF XY:

0.469

AC XY:

34857

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.505

AC:

20963

AN:

41490

American (AMR)

AF:

0.483

AC:

7382

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1455

AN:

3472

East Asian (EAS)

AF:

0.737

AC:

3800

AN:

5154

South Asian (SAS)

AF:

0.550

AC:

2654

AN:

4824

European-Finnish (FIN)

AF:

0.438

AC:

4645

AN:

10602

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.414

AC:

28114

AN:

67976

Other (OTH)

AF:

0.453

AC:

958

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1994

3988

5981

7975

9969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.433

Hom.:

64375

Bravo

AF:

0.467

Asia WGS

AF:

0.570

AC:

1985

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

7.9

(source)

DANN

Benign

0.89

PhyloP100

0.20

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