dbSNP rs757948496: SERTAD3:p.Arg54Thr (chr19-40441920-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_203344.3(SERTAD3):c.161G>C(p.Arg54Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000422 in 1,420,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R54K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

SERTAD3
NM_203344.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67

Publications

0 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: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.855

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.161G>C	p.Arg54Thr	missense	Exon 2 of 2	NP_976219.1	Q9UJW9
	SERTAD3	NM_013368.4		c.161G>C	p.Arg54Thr	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.161G>C	p.Arg54Thr	missense	Exon 2 of 2	ENSP00000325414.2	Q9UJW9
SERTAD3	ENST00000392028.9	TSL:1	c.161G>C	p.Arg54Thr	missense	Exon 2 of 2	ENSP00000375882.3
SERTAD3	ENST00000865349.1		c.161G>C	p.Arg54Thr	missense	Exon 3 of 3	ENSP00000535408.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000946

AC:

AN:

211328

AF XY:

0.00000883

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000422

AC:

AN:

1420890

Hom.:

Cov.:

AF XY:

0.00000427

AC XY:

AN XY:

703368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32260

American (AMR)

AF:

0.00

AC:

AN:

37954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23054

East Asian (EAS)

AF:

0.00

AC:

AN:

39336

South Asian (SAS)

AF:

0.0000754

AC:

AN:

79626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092588

Other (OTH)

AF:

0.00

AC:

AN:

58570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.80

M_CAP

Benign

0.0073

MetaRNN

Pathogenic

0.85

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.0

PhyloP100

2.7

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.31

Sift

Uncertain

0.015

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.80

MutPred

0.78

Loss of MoRF binding (P = 0.0256)

MVP

0.28

MPC

0.88

ClinPred

0.65

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.51

gMVP

0.69

Mutation Taster

=68/32

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