Variant 5-154446640-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024632.6(SAP30L):c.36A>C(p.Glu12Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000392 in 1,528,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

SAP30L
NM_024632.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

SAP30L (HGNC:25663): (SAP30 like) Enables several functions, including non-sequence-specific DNA binding activity, bending; phosphatidylinositol phosphate binding activity; and zinc ion binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in fibrillar center and nucleoplasm. Part of histone deacetylase complex. [provided by Alliance of Genome Resources, Apr 2022]

SAP30L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020427346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAP30L	NM_024632.6 linkuse as main transcript	c.36A>C	p.Glu12Asp	missense_variant	1/4	ENST00000297109.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAP30L	ENST00000297109.11 linkuse as main transcript	c.36A>C	p.Glu12Asp	missense_variant	1/4	1	NM_024632.6	P1	Q9HAJ7-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000322

AC:

AN:

124284

Hom.:

AF XY:

0.0000146

AC XY:

AN XY:

68544

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000865

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1376982

Hom.:

Cov.:

AF XY:

0.0000309

AC XY:

AN XY:

679228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000457

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000229

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.36A>C (p.E12D) alteration is located in exon 1 (coding exon 1) of the SAP30L gene. This alteration results from a A to C substitution at nucleotide position 36, causing the glutamic acid (E) at amino acid position 12 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Benign

0.77

DEOGEN2

Benign

0.0058

T;.;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.80

T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.3

N;N;N

MutationTaster

Benign

0.89

D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.12

N;N;N

REVEL

Benign

0.10

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.79

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.045

MutPred

0.10

Loss of glycosylation at P14 (P = 0.1069);Loss of glycosylation at P14 (P = 0.1069);Loss of glycosylation at P14 (P = 0.1069);

MVP

0.043

MPC

0.49

ClinPred

0.062

GERP RS

2.3

Varity_R

0.050

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over