Genetic Variant SERTAD3:p.Arg43Ser (chr19-40441954-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_203344.3(SERTAD3):c.127C>A(p.Arg43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000776 in 1,418,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

SERTAD3
NM_203344.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.16

Publications

8 publications found

Variant links:

Genes affected

SERTAD3 (HGNC:17931): (SERTA domain containing 3) The protein encoded by this gene was identified in a yeast two-hybrid assay employing the second subunit of human replication protein A as bait. It is localized to the nucleus and its expression is significantly higher in cancer cell lines compared to normal cell lines. This protein has also been shown to be a strong transcriptional co-activator. Alternative splicing has been observed at this locus and two variants, both encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

SERTAD3 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.14710525).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203344.3. 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
	SERTAD3	NM_203344.3	MANE Select	c.127C>A	p.Arg43Ser	missense	Exon 2 of 2	NP_976219.1	Q9UJW9
	SERTAD3	NM_013368.4		c.127C>A	p.Arg43Ser	missense	Exon 2 of 2	NP_037500.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERTAD3	ENST00000322354.4	TSL:1 MANE Select	c.127C>A	p.Arg43Ser	missense	Exon 2 of 2	ENSP00000325414.2	Q9UJW9
SERTAD3	ENST00000392028.9	TSL:1	c.127C>A	p.Arg43Ser	missense	Exon 2 of 2	ENSP00000375882.3
SERTAD3	ENST00000865349.1		c.127C>A	p.Arg43Ser	missense	Exon 3 of 3	ENSP00000535408.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

210436

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000776

AC:

AN:

1418414

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

701976

show subpopulations

African (AFR)

AF:

0.000218

AC:

AN:

32142

American (AMR)

AF:

0.00

AC:

AN:

37352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22982

East Asian (EAS)

AF:

0.00

AC:

AN:

39346

South Asian (SAS)

AF:

0.00

AC:

AN:

79198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51738

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091638

Other (OTH)

AF:

0.0000513

AC:

AN:

58478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.21

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.062

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.67

M_CAP

Benign

0.0018

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

1.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.6

REVEL

Benign

0.045

Sift

Uncertain

0.026

Sift4G

Pathogenic

0.0

Polyphen

0.018

Vest4

0.20

MutPred

0.49

Loss of MoRF binding (P = 0.018)

MVP

0.21

MPC

0.26

ClinPred

0.20

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.18

gMVP

0.32

Mutation Taster

=79/21

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over