rs2251954

chr3-45690292-T-Cchr3-45690292-T-G

Variant summary

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

The NM_014016.5(SACM1L):c.32+795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,166 control chromosomes in the GnomAD database, including 18,098 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 (18097 hom., cov: 33)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: SACM1L NM_014016.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=-0.81).
• 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	UniProt
SACM1L	NM_014016.5	c.32+795T>C		intron_variant		ENST00000389061.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SACM1L	ENST00000389061.10	c.32+795T>C		intron_variant		1	NM_014016.5	P1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73074 AN: 152044 Hom.: 18085 Cov.: 33

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.481 AC: 73119 AN: 152162 Hom.: 18097 Cov.: 33 AF XY: 0.476 AC XY: 35425 AN XY: 74388

Gnomad4 AFR AF: 0.420

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.506

Alfa AF: 0.491 Hom.: 3198

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	-0.81
Cadd	Benign	2.2
Dann	Benign	0.79

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: rs2251954; hg19: chr3-45731784;