dbSNP rs11062: SMYD4:c.*1568C>T (chr17-1779718-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_052928.3(SMYD4):c.*1568C>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 0.375 in 152,194 control chromosomes in the GnomAD database, including 10,976 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 0.38 ( 10970 hom., cov: 33)

Exomes 𝑓: 0.39 ( 6 hom. )

Consequence

SMYD4
NM_052928.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.333

Publications

29 publications found

Variant links:

Genes affected

SMYD4 (HGNC:21067): (SET and MYND domain containing 4) Predicted to enable metal ion binding activity and methyltransferase activity. Involved in heart development. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SMYD4 links:

Genome browser will be placed here

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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SMYD4	NM_052928.3 link	c.*1568C>T	3_prime_UTR_variant	Exon 11 of 11	ENST00000305513.12	NP_443160.2	Q8IYR2
SMYD4	XM_024450560.2 link	c.*1568C>T	3_prime_UTR_variant	Exon 11 of 11		XP_024306328.1
SMYD4	XM_047435291.1 link	c.*1568C>T	3_prime_UTR_variant	Exon 10 of 10		XP_047291247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513.12 link	c.*1568C>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_052928.3	ENSP00000304360.7		Q8IYR2

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

57004

AN:

151984

Hom.:

10954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.381

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.356

GnomAD4 exome

AF:

0.391

AC:

AN:

Hom.:

Cov.:

AF XY:

0.407

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.405

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.375

AC:

57062

AN:

152102

Hom.:

10970

Cov.:

AF XY:

0.381

AC XY:

28321

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.380

AC:

15756

AN:

41504

American (AMR)

AF:

0.466

AC:

7121

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

1321

AN:

3470

East Asian (EAS)

AF:

0.507

AC:

2624

AN:

5176

South Asian (SAS)

AF:

0.426

AC:

2056

AN:

4824

European-Finnish (FIN)

AF:

0.428

AC:

4521

AN:

10554

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22611

AN:

67982

Other (OTH)

AF:

0.357

AC:

754

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1855

3710

5565

7420

9275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.348

Hom.:

30388

Bravo

AF:

0.379

Asia WGS

AF:

0.476

AC:

1652

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.6

(source)

DANN

Benign

0.72

PhyloP100

0.33

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