4-143514055-C-A

Variant names:

• chr4-143514055-C-A
• rs1462902570
• NM_003601.4:c.131C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003601.4(SMARCA5):​c.131C>A​(p.Ala44Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,407,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A44V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SMARCA5 NM_003601.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098159075).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003601.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA5	NM_003601.4	MANE Select	c.131C>A	p.Ala44Glu	missense	Exon 1 of 24	NP_003592.3
	SMARCA5-AS1	NR_104027.1		n.564G>T		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCA5	ENST00000283131.4	TSL:1 MANE Select	c.131C>A	p.Ala44Glu	missense	Exon 1 of 24	ENSP00000283131.3	O60264
	SMARCA5-AS1	ENST00000500800.3	TSL:1	n.362G>T		non_coding_transcript_exon	Exon 2 of 2
	SMARCA5	ENST00000940952.1		c.131C>A	p.Ala44Glu	missense	Exon 1 of 25	ENSP00000611011.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000614 AC: 1 AN: 162956 AF XY: 0.0000110

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000144

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1407746 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 697350

African (AFR) AF: 0.00 AC: 0 AN: 31930

American (AMR) AF: 0.00 AC: 0 AN: 39238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25236

East Asian (EAS) AF: 0.00 AC: 0 AN: 37198

South Asian (SAS) AF: 0.00 AC: 0 AN: 82082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1093492

Other (OTH) AF: 0.00 AC: 0 AN: 58690

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	19
DANN	Benign	0.73
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.58
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	0.87	N
REVEL	Benign	0.24
Sift	Benign	0.80	T
Sift4G	Benign	1.0	T
Polyphen		0.020	B
Vest4		0.29
MutPred		0.29		Loss of catalytic residue at Q43 (P = 0.1006)
MVP		0.37
MPC		0.24
ClinPred		0.10	T
GERP RS		3.2
PromoterAI		0.059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.16
gMVP		0.39
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs1462902570; hg19: chr4-144435208;