rs2673057

Positions:

• chr3-45694238-T-A

Variant summary

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

The NM_014016.5(SACM1L):​c.32+4741T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,996 control chromosomes in the GnomAD database, including 18,221 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 (18221 hom., cov: 31)
• Consequence: SACM1L NM_014016.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858

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]

SACM1L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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+4741T>A		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+4741T>A		intron_variant		1	NM_014016.5	ENSP00000373713.4

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73279 AN: 151878 Hom.: 18210 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.505

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.482 AC: 73322 AN: 151996 Hom.: 18221 Cov.: 31 AF XY: 0.478 AC XY: 35523 AN XY: 74294

Gnomad4 AFR AF: 0.427

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: 0.527

Gnomad4 OTH AF: 0.508

Alfa AF: 0.499 Hom.: 2359

Bravo AF: 0.480

Asia WGS AF: 0.334 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.87

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: rs2673057; hg19: chr3-45735730;