Genetic Variant SERTAD3:p.Arg70His (chr19-40441872-C-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_203344.3(SERTAD3):c.209G>A(p.Arg70His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000393 in 1,576,792 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 (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SERTAD3
NM_203344.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0960

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.100038975).

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.209G>A	p.Arg70His	missense	Exon 2 of 2	NP_976219.1	Q9UJW9
	SERTAD3	NM_013368.4		c.209G>A	p.Arg70His	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.209G>A	p.Arg70His	missense	Exon 2 of 2	ENSP00000325414.2	Q9UJW9
SERTAD3	ENST00000392028.9	TSL:1	c.209G>A	p.Arg70His	missense	Exon 2 of 2	ENSP00000375882.3
SERTAD3	ENST00000865349.1		c.209G>A	p.Arg70His	missense	Exon 3 of 3	ENSP00000535408.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000468

AC:

AN:

213832

AF XY:

0.00000871

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000573

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000400

AC:

AN:

1424682

Hom.:

Cov.:

AF XY:

0.0000425

AC XY:

AN XY:

705298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32458

American (AMR)

AF:

0.00

AC:

AN:

39010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23328

East Asian (EAS)

AF:

0.0000508

AC:

AN:

39358

South Asian (SAS)

AF:

0.00

AC:

AN:

80400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5532

European-Non Finnish (NFE)

AF:

0.0000503

AC:

AN:

1093900

Other (OTH)

AF:

0.00

AC:

AN:

58698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.0000329

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

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:

0.0000659

Hom.:

Bravo

AF:

0.0000340

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

0.064

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.4

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.27

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.71

M_CAP

Benign

0.0016

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.096

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.1

REVEL

Benign

0.14

Sift

Benign

0.19

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.050

MutPred

0.47

Loss of methylation at R70 (P = 0.0471)

MVP

0.22

MPC

0.22

ClinPred

0.050

GERP RS

-9.7

Varity_R

0.050

gMVP

0.12

Mutation Taster

=97/3

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over