Genetic Variant SESTD1:p.Thr534Thr (chr2-179116713-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_178123.5(SESTD1):c.1602G>A(p.Thr534Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,614,096 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

SESTD1
NM_178123.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.853

Publications

3 publications found

Variant links:

Genes affected

SESTD1 (HGNC:18379): (SEC14 and spectrin domain containing 1) Enables phosphatidylinositol-3,4-bisphosphate binding activity and phospholipid binding activity. Involved in negative regulation of calcium ion transmembrane transport via high voltage-gated calcium channel. Located in intermediate filament cytoskeleton. Colocalizes with calcium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

SESTD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 2-179116713-C-T is Benign according to our data. Variant chr2-179116713-C-T is described in ClinVar as Benign. ClinVar VariationId is 770877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.853 with no splicing effect.

BS2

High AC in GnomAd4 at 267 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178123.5. 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
	SESTD1	NM_178123.5	MANE Select	c.1602G>A	p.Thr534Thr	synonymous	Exon 15 of 18	NP_835224.3	Q86VW0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SESTD1	ENST00000428443.8	TSL:1 MANE Select	c.1602G>A	p.Thr534Thr	synonymous	Exon 15 of 18	ENSP00000415332.2	Q86VW0
SESTD1	ENST00000949563.1		c.1617G>A	p.Thr539Thr	synonymous	Exon 15 of 18	ENSP00000619622.1
SESTD1	ENST00000854639.1		c.1602G>A	p.Thr534Thr	synonymous	Exon 16 of 19	ENSP00000524698.1

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

267

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00808

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00216

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00197

AC:

495

AN:

251200

AF XY:

0.00194

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00200

AC:

2918

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1420

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33478

American (AMR)

AF:

0.00210

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00991

AC:

259

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00215

AC:

2391

AN:

1111978

Other (OTH)

AF:

0.00222

AC:

134

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

157

313

470

626

783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<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:

0.00175

AC:

267

AN:

152306

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41576

American (AMR)

AF:

0.00333

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00808

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00216

AC:

147

AN:

68022

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.00190

Hom.:

Bravo

AF:

0.00187

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.00191

EpiControl

AF:

0.00243

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

5.3

(source)

DANN

Benign

0.63

PhyloP100

-0.85

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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