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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032701.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KMT5C	NM_032701.4	MANE Select	c.*622C>A	3_prime_UTR	Exon 9 of 9	NP_116090.2
KMT5C	NM_001438948.1		c.*622C>A	3_prime_UTR	Exon 9 of 9	NP_001425877.1
KMT5C	NM_001438949.1		c.*622C>A	3_prime_UTR	Exon 8 of 8	NP_001425878.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KMT5C	ENST00000255613.8	TSL:1 MANE Select	c.*622C>A	3_prime_UTR	Exon 9 of 9	ENSP00000255613.3	Q86Y97-1
KMT5C	ENST00000630497.1	TSL:1	c.*622C>A	3_prime_UTR	Exon 7 of 7	ENSP00000486397.1	A0A0D9SF94
KMT5C	ENST00000943506.1		c.*622C>A	3_prime_UTR	Exon 9 of 9	ENSP00000613565.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over