Genetic Variant SERTAD1:p.Leu128Met (chr19-40423165-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013376.4(SERTAD1):c.382C>A(p.Leu128Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,602,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SERTAD1
NM_013376.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.160

Publications

0 publications found

Variant links:

Genes affected

SERTAD1 (HGNC:17932): (SERTA domain containing 1) Predicted to be involved in epigenetic maintenance of chromatin in transcription-competent conformation. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SERTAD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24965349).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013376.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SERTAD1	NM_013376.4	MANE Select	c.382C>A	p.Leu128Met	missense	Exon 2 of 2	NP_037508.2	Q9UHV2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERTAD1	ENST00000357949.5	TSL:1 MANE Select	c.382C>A	p.Leu128Met	missense	Exon 2 of 2	ENSP00000350633.4	Q9UHV2
SERTAD1	ENST00000869921.1		c.382C>A	p.Leu128Met	missense	Exon 2 of 2	ENSP00000539980.1
SERTAD1	ENST00000869922.1		c.382C>A	p.Leu128Met	missense	Exon 2 of 2	ENSP00000539981.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000865

AC:

AN:

231086

AF XY:

0.00000795

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1450332

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

720174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33296

American (AMR)

AF:

0.00

AC:

AN:

43260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25806

East Asian (EAS)

AF:

0.00

AC:

AN:

39266

South Asian (SAS)

AF:

0.00

AC:

AN:

84676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

1106114

Other (OTH)

AF:

0.0000167

AC:

AN:

59858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41474

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.64

M_CAP

Benign

0.019

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.7

PhyloP100

0.16

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.40

REVEL

Benign

0.18

Sift

Uncertain

0.014

Sift4G

Benign

0.27

Polyphen

1.0

Vest4

0.20

MutPred

0.36

Loss of helix (P = 0.2022)

MVP

0.61

MPC

1.0

ClinPred

0.44

GERP RS

-4.2

Varity_R

0.063

gMVP

0.38

Mutation Taster

=87/13

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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