rs372599773

Variant names:

• chr2-179124483-C-A
• rs372599773
• NM_178123.5:c.1048G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-179124483-C-A
• chr2-179124483-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178123.5(SESTD1):​c.1048G>T​(p.Val350Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. V350M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SESTD1 NM_178123.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.60
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16919702).

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.1048G>T	p.Val350Leu	missense	Exon 11 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.1048G>T	p.Val350Leu	missense	Exon 11 of 18	ENSP00000415332.2	Q86VW0
	SESTD1	ENST00000949563.1		c.1048G>T	p.Val350Leu	missense	Exon 11 of 18	ENSP00000619622.1
	SESTD1	ENST00000854639.1		c.1048G>T	p.Val350Leu	missense	Exon 12 of 19	ENSP00000524698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.044
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.093
Sift	Benign	0.13	T
Sift4G	Benign	0.38	T
Polyphen		0.0020	B
Vest4		0.29
MutPred		0.59		Loss of helix (P = 0.079)
MVP		0.068
MPC		0.56
ClinPred		0.76	D
GERP RS		4.9
Varity_R		0.16
gMVP		0.25
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs372599773; hg19: chr2-179989210;