2-179112815-C-T

Variant names:

• chr2-179112815-C-T
• rs777219502
• NM_178123.5:c.1870G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_178123.5(SESTD1):​c.1870G>A​(p.Ala624Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. A624S) 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: 1.40
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030942708).

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.1870G>A	p.Ala624Thr	missense	Exon 17 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.1870G>A	p.Ala624Thr	missense	Exon 17 of 18	ENSP00000415332.2	Q86VW0
	SESTD1	ENST00000949563.1		c.1885G>A	p.Ala629Thr	missense	Exon 17 of 18	ENSP00000619622.1
	SESTD1	ENST00000854639.1		c.1870G>A	p.Ala624Thr	missense	Exon 18 of 19	ENSP00000524698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249992 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Benign	0.81
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.025
Sift	Benign	0.60	T
Sift4G	Benign	0.87	T
Polyphen		0.0	B
Vest4		0.083
MutPred		0.29		Gain of phosphorylation at A624 (P = 0.0322)
MVP		0.043
MPC		0.55
ClinPred		0.16	T
GERP RS		2.6
Varity_R		0.052
gMVP		0.33
Mutation Taster		=94/6	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: rs777219502; hg19: chr2-179977542;