Genetic Variant SERTAD1:p.Ala149Thr (chr19-40423102-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_013376.4(SERTAD1):c.445G>A(p.Ala149Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A149P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SERTAD1
NM_013376.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0590

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039390177).

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.445G>A	p.Ala149Thr	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.445G>A	p.Ala149Thr	missense	Exon 2 of 2	ENSP00000350633.4	Q9UHV2
SERTAD1	ENST00000869921.1		c.445G>A	p.Ala149Thr	missense	Exon 2 of 2	ENSP00000539980.1
SERTAD1	ENST00000869922.1		c.445G>A	p.Ala149Thr	missense	Exon 2 of 2	ENSP00000539981.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1444120

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33166

American (AMR)

AF:

0.00

AC:

AN:

41862

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25642

East Asian (EAS)

AF:

0.00

AC:

AN:

38896

South Asian (SAS)

AF:

0.0000120

AC:

AN:

83592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1104138

Other (OTH)

AF:

0.0000168

AC:

AN:

59664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.51

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.059

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.68

M_CAP

Benign

0.0056

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PhyloP100

-0.059

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.21

REVEL

Benign

0.023

Sift

Benign

0.70

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.022

MutPred

0.26

Gain of glycosylation at A149 (P = 0.01)

MVP

0.20

MPC

0.29

ClinPred

0.021

GERP RS

-6.4

Varity_R

0.013

gMVP

0.35

Mutation Taster

=100/0

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over