4-143513981-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_003601.4(SMARCA5):c.57G>T(p.Lys19Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,408,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000064 ( 0 hom. )

Consequence

SMARCA5
NM_003601.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.572

Variant links:

Genes affected

SMARCA5 (HGNC:11101): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 5) 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 protein encoded by this gene is a component of the chromatin remodeling and spacing factor RSF, a facilitator of the transcription of class II genes by RNA polymerase II. The encoded protein is similar in sequence to the Drosophila ISWI chromatin remodeling protein. [provided by RefSeq, Jul 2008]

SMARCA5 links:

SMARCA5-AS1 (HGNC:39982): (SMARCA5 antisense RNA 1)

SMARCA5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP2

Missense variant where missense usually causes diseases, SMARCA5

BP4

Computational evidence support a benign effect (MetaRNN=0.15654203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMARCA5	NM_003601.4 linkuse as main transcript	c.57G>T	p.Lys19Asn	missense_variant	1/24	ENST00000283131.4
SMARCA5-AS1	NR_104027.1 linkuse as main transcript	n.638C>A		non_coding_transcript_exon_variant	2/2
SMARCA5	XM_047416323.1 linkuse as main transcript	c.57G>T	p.Lys19Asn	missense_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMARCA5	ENST00000283131.4 linkuse as main transcript	c.57G>T	p.Lys19Asn	missense_variant	1/24	1	NM_003601.4	P1
SMARCA5-AS1	ENST00000500800.2 linkuse as main transcript	n.436C>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000184

AC:

AN:

162770

Hom.:

AF XY:

0.0000111

AC XY:

AN XY:

90388

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:

0.0000438

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000639

AC:

AN:

1408952

Hom.:

Cov.:

AF XY:

0.00000573

AC XY:

AN XY:

698034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000823

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000175

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2023

The c.57G>T (p.K19N) alteration is located in exon 1 (coding exon 1) of the SMARCA5 gene. This alteration results from a G to T substitution at nucleotide position 57, causing the lysine (K) at amino acid position 19 to be replaced by an asparagine (N). 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

0.26

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.82

DEOGEN2

Benign

0.21

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.020

REVEL

Benign

0.14

Sift

Benign

0.24

Sift4G

Benign

0.52

Polyphen

0.80

Vest4

0.24

MutPred

0.25

Loss of ubiquitination at K19 (P = 0.0012);

MVP

0.59

MPC

0.25

ClinPred

0.092

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.35

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

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