Genetic Variant NM_014016.5:c.946C>T (chr3-45731325-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014016.5(SACM1L):c.946C>T(p.Pro316Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P316A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SACM1L
NM_014016.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Publications

0 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014016.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SACM1L	NM_014016.5	MANE Select	c.946C>T	p.Pro316Ser	missense	Exon 12 of 20	NP_054735.3
SACM1L	NM_001319071.2		c.946C>T	p.Pro316Ser	missense	Exon 12 of 20	NP_001306000.1	A0A5F9ZHN7
SACM1L	NM_001319072.2		c.763C>T	p.Pro255Ser	missense	Exon 11 of 19	NP_001306001.1	Q9NTJ5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SACM1L	ENST00000389061.10	TSL:1 MANE Select	c.946C>T	p.Pro316Ser	missense	Exon 12 of 20	ENSP00000373713.4	Q9NTJ5-1
SACM1L	ENST00000455997.5	TSL:1	n.637C>T		non_coding_transcript_exon	Exon 12 of 20	ENSP00000389975.1	F8WDN7
SACM1L	ENST00000672858.2		c.946C>T	p.Pro316Ser	missense	Exon 12 of 20	ENSP00000500542.2	A0A5F9ZHN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.015

Eigen

Benign

0.073

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

PhyloP100

7.6

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.040

REVEL

Benign

0.15

Sift

Benign

0.69

Sift4G

Benign

0.68

Polyphen

0.0080

Vest4

0.69

MutPred

0.51

Gain of disorder (P = 0.097)

MVP

0.29

MPC

0.42

ClinPred

0.80

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.079

gMVP

0.56

Mutation Taster

=39/61

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over