Variant chr2-73221884-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006062.3(SMYD5):c.596A>G(p.Asn199Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000408 in 1,613,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 1 hom. )

Consequence

SMYD5
NM_006062.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84

Variant links:

Genes affected

SMYD5 (HGNC:16258): (SMYD family member 5) Predicted to enable histone methyltransferase activity (H4-K20 specific). Involved in negative regulation of transposition and regulation of stem cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

SMYD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31002736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD5	NM_006062.3 linkuse as main transcript	c.596A>G	p.Asn199Ser	missense_variant	6/13	ENST00000389501.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SMYD5	ENST00000389501.9 linkuse as main transcript	c.596A>G	p.Asn199Ser	missense_variant	6/13	1	NM_006062.3	P1
SMYD5	ENST00000474652.1 linkuse as main transcript	n.715A>G		non_coding_transcript_exon_variant	6/6	5
SMYD5	ENST00000477038.1 linkuse as main transcript	n.118A>G		non_coding_transcript_exon_variant	2/4	5
SMYD5	ENST00000258100.8 linkuse as main transcript	c.*364A>G		3_prime_UTR_variant, NMD_transcript_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000354

AC:

AN:

251488

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000721

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000404

AC:

591

AN:

1461670

Hom.:

Cov.:

AF XY:

0.000432

AC XY:

314

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.000510

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000447

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000955

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000652

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 28, 2022

The c.596A>G (p.N199S) alteration is located in exon 6 (coding exon 6) of the SMYD5 gene. This alteration results from a A to G substitution at nucleotide position 596, causing the asparagine (N) at amino acid position 199 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

M_CAP

Benign

0.045

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.22

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.53

MVP

0.83

MPC

0.98

ClinPred

0.49

GERP RS

5.5

Varity_R

0.22

gMVP

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over