rs2742417

Variant names:

• chr3-45689959-C-G
• rs2742417
• ENST00000455997.5:n.-706C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-45689959-C-G
• chr3-45689959-C-T

Variant summary

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

The ENST00000455997.5(SACM1L):​n.-706C>G variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SACM1L ENST00000455997.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 23 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: 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 (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SACM1L	NM_014016.5	c.32+462C>G		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+462C>G		intron_variant	Intron 1 of 19	1	NM_014016.5	ENSP00000373713.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 15130 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 7814

African (AFR) AF: 0.00 AC: 0 AN: 304

American (AMR) AF: 0.00 AC: 0 AN: 1482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 338

East Asian (EAS) AF: 0.00 AC: 0 AN: 718

South Asian (SAS) AF: 0.00 AC: 0 AN: 1872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 36

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 9176

Other (OTH) AF: 0.00 AC: 0 AN: 798

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.43
DANN	Benign	0.58
PhyloP100		-1.2
PromoterAI		0.050	Neutral

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: rs2742417; hg19: chr3-45731451;