3-45689959-C-T

Position:

• chr3-45689959-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000389061.10(SACM1L):​c.32+462C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 167,192 control chromosomes in the GnomAD database, including 19,752 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.48 (18015 hom., cov: 34)
  • Exomes 𝑓: 0.47 (1737 hom.)
• Consequence: SACM1L ENST00000389061.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

Genes affected

SACM1L (HGNC:17059): (SAC1 like phosphatidylinositide phosphatase) This gene encodes an integral membrane protein, which is localized to the endoplasmic reticulum, and functions as a phosphoinositide phosphatase that hydrolyzes phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, and phosphatidylinositol 3,5-bisphosphate. Deletion of this gene in mouse results in preimplantation lethality. Other studies suggest that this gene is also involved in the organization of golgi membranes and mitotic spindles. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame, downstream translation termination codon via a stop codon readthrough mechanism.[provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SACM1L	NM_014016.5	c.32+462C>T		intron_variant		ENST00000389061.10	NP_054735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SACM1L	ENST00000389061.10	c.32+462C>T		intron_variant		1	NM_014016.5	ENSP00000373713	P1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72917 AN: 151994 Hom.: 18004 Cov.: 34

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.471 AC: 7109 AN: 15078 Hom.: 1737 Cov.: 0 AF XY: 0.469 AC XY: 3654 AN XY: 7784

Gnomad4 AFR exome AF: 0.421

Gnomad4 AMR exome AF: 0.443

Gnomad4 ASJ exome AF: 0.645

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.495

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.476

GnomAD4 genome AF: 0.480 AC: 72960 AN: 152114 Hom.: 18015 Cov.: 34 AF XY: 0.475 AC XY: 35333 AN XY: 74388

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.504

Alfa AF: 0.522 Hom.: 20752

Bravo AF: 0.478

Asia WGS AF: 0.335 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.58
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs2742417; hg19: chr3-45731451;