rs2673057

Variant names:

• chr3-45694238-T-A
• rs2673057
• NM_014016.5:c.32+4741T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SACM1L	NM_014016.5	c.32+4741T>A		intron_variant	Intron 1 of 19	ENST00000389061.10	NP_054735.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SACM1L	ENST00000389061.10	c.32+4741T>A		intron_variant	Intron 1 of 19	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

African (AFR) AF: 0.427 AC: 17675 AN: 41430

American (AMR) AF: 0.479 AC: 7323 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2121 AN: 3472

East Asian (EAS) AF: 0.237 AC: 1229 AN: 5176

South Asian (SAS) AF: 0.357 AC: 1717 AN: 4816

European-Finnish (FIN) AF: 0.544 AC: 5736 AN: 10550

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35841 AN: 67962

Other (OTH) AF: 0.508 AC: 1072 AN: 2112

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
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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: rs2673057; hg19: chr3-45735730;