2-179115174-C-T

Variant names:

• chr2-179115174-C-T
• rs755373339
• NM_178123.5:c.1730G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_178123.5(SESTD1):​c.1730G>A​(p.Gly577Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G577V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SESTD1 NM_178123.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1730G>A	p.Gly577Glu	missense	Exon 16 of 18	NP_835224.3	Q86VW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SESTD1	ENST00000428443.8	TSL:1 MANE Select	c.1730G>A	p.Gly577Glu	missense	Exon 16 of 18	ENSP00000415332.2	Q86VW0
	SESTD1	ENST00000949563.1		c.1745G>A	p.Gly582Glu	missense	Exon 16 of 18	ENSP00000619622.1
	SESTD1	ENST00000854639.1		c.1730G>A	p.Gly577Glu	missense	Exon 17 of 19	ENSP00000524698.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461658 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727116

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111914

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.5
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.93	N
REVEL	Uncertain	0.33
Sift	Benign	0.12	T
Sift4G	Benign	0.45	T
Polyphen		1.0	D
Vest4		0.80
MutPred		0.31		Loss of MoRF binding (P = 0.0443)
MVP		0.24
MPC		0.83
ClinPred		0.69	D
GERP RS		5.7
Varity_R		0.37
gMVP		0.62
Mutation Taster		=22/78	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs755373339; hg19: chr2-179979901;