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

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SESTD1	NM_178123.5 link	c.1602G>A	p.Thr534Thr	synonymous_variant	Exon 15 of 18	ENST00000428443.8	NP_835224.3	Q86VW0B3KTX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SESTD1	ENST00000428443.8 link	c.1602G>A	p.Thr534Thr	synonymous_variant	Exon 15 of 18	1	NM_178123.5	ENSP00000415332.2	Q86VW0
SESTD1	ENST00000335289.5 link	n.*319G>A		non_coding_transcript_exon_variant	Exon 7 of 10	5		ENSP00000334183.5	H7BXT9
SESTD1	ENST00000446758.5 link	n.537G>A		non_coding_transcript_exon_variant	Exon 5 of 8	2		ENSP00000410632.1	H0Y774
SESTD1	ENST00000335289.5 link	n.*319G>A		3_prime_UTR_variant	Exon 7 of 10	5		ENSP00000334183.5	H7BXT9

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

GnomAD3 exomes

AF:

0.00197

AC:

495

AN:

251200

Hom.:

AF XY:

0.00194

AC XY:

264

AN XY:

135760

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 SAS exome

AF:

0.0000980

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

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00991

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00222

GnomAD4 genome

AF:

0.00175

AC:

267

AN:

152306

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00808

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.00187

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.00191

EpiControl

AF:

0.00243

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

5.3

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over