chr2-216414745-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014140.4(SMARCAL1):​c.41A>T​(p.Glu14Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SMARCAL1
NM_014140.4 missense

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 6.60
Variant links:
Genes affected
SMARCAL1 (HGNC:11102): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41867805).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMARCAL1NM_014140.4 linkuse as main transcriptc.41A>T p.Glu14Val missense_variant 3/18 ENST00000357276.9
SMARCAL1NM_001127207.2 linkuse as main transcriptc.41A>T p.Glu14Val missense_variant 3/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMARCAL1ENST00000357276.9 linkuse as main transcriptc.41A>T p.Glu14Val missense_variant 3/182 NM_014140.4 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152200
Hom.:
0
Cov.:
33
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152200
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74362
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 02, 2022The c.41A>T (p.E14V) alteration is located in exon 3 (coding exon 1) of the SMARCAL1 gene. This alteration results from a A to T substitution at nucleotide position 41, causing the glutamic acid (E) at amino acid position 14 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Schimke immuno-osseous dysplasia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 01, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.47
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
T;T;.;T;T;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.83
T;.;T;.;T;T
M_CAP
Pathogenic
0.31
D
MetaRNN
Benign
0.42
T;T;T;T;T;T
MetaSVM
Pathogenic
0.88
D
MutationAssessor
Uncertain
2.6
.;M;.;.;M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-7.0
D;N;D;D;N;D
REVEL
Benign
0.28
Sift
Pathogenic
0.0
D;D;D;.;D;D
Sift4G
Pathogenic
0.0
D;D;D;.;D;D
Polyphen
1.0
.;D;.;.;D;.
Vest4
0.45
MutPred
0.24
Loss of ubiquitination at K12 (P = 0.0333);Loss of ubiquitination at K12 (P = 0.0333);Loss of ubiquitination at K12 (P = 0.0333);Loss of ubiquitination at K12 (P = 0.0333);Loss of ubiquitination at K12 (P = 0.0333);Loss of ubiquitination at K12 (P = 0.0333);
MVP
0.97
MPC
0.90
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.74
gMVP
0.64

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.

Other links and lift over

dbSNP: rs1693548931; hg19: chr2-217279468; API