Genetic Variant SACM1L:p.Tyr6Phe (chr3-45689482-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014016.5(SACM1L):c.17A>T(p.Tyr6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000841 in 1,427,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Consequence

SACM1L
NM_014016.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06386888).

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.17A>T	p.Tyr6Phe	missense	Exon 1 of 20	NP_054735.3
SACM1L	NM_001319071.2		c.17A>T	p.Tyr6Phe	missense	Exon 1 of 20	NP_001306000.1	A0A5F9ZHN7
SACM1L	NM_001319072.2		c.-39A>T		5_prime_UTR	Exon 1 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.17A>T	p.Tyr6Phe	missense	Exon 1 of 20	ENSP00000373713.4	Q9NTJ5-1
SACM1L	ENST00000455997.5	TSL:1	n.-1183A>T		non_coding_transcript_exon	Exon 1 of 20	ENSP00000389975.1	F8WDN7
SACM1L	ENST00000455997.5	TSL:1	n.-1183A>T		5_prime_UTR	Exon 1 of 20	ENSP00000389975.1	F8WDN7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000632

AC:

AN:

189862

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000841

AC:

AN:

1427286

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

706338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32990

American (AMR)

AF:

0.000312

AC:

AN:

38496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

38236

South Asian (SAS)

AF:

0.00

AC:

AN:

81550

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50070

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095790

Other (OTH)

AF:

0.00

AC:

AN:

59120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000170

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.068

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.68

M_CAP

Benign

0.065

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

PhyloP100

2.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.1

REVEL

Benign

0.090

Sift

Benign

0.14

Sift4G

Benign

0.15

Polyphen

0.0030

Vest4

0.42

MutPred

0.52

Gain of glycosylation at Y6 (P = 0.0257)

MVP

0.38

MPC

0.39

ClinPred

0.11

GERP RS

4.3

PromoterAI

-0.17

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.0

Varity_R

0.24

gMVP

0.70

Mutation Taster

=50/50

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over