4-143513937-G-C

Variant names:

• chr4-143513937-G-C
• rs926979803
• NM_003601.4:c.13G>C

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.13G>C​(p.Ala5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. A5S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SMARCA5 NM_003601.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619
• 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=0.13572043).

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.13G>C	p.Ala5Pro	missense	Exon 1 of 24	NP_003592.3
	SMARCA5-AS1	NR_104027.1		n.682C>G		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.13G>C	p.Ala5Pro	missense	Exon 1 of 24	ENSP00000283131.3	O60264
	SMARCA5-AS1	ENST00000500800.3	TSL:1	n.480C>G		non_coding_transcript_exon	Exon 2 of 2
	SMARCA5	ENST00000940952.1		c.13G>C	p.Ala5Pro	missense	Exon 1 of 25	ENSP00000611011.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.62
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.31	N
REVEL	Uncertain	0.29
Sift	Benign	0.14	T
Sift4G	Benign	0.25	T
Polyphen		0.056	B
Vest4		0.16
MutPred		0.17		Gain of glycosylation at A5 (P = 0.0106)
MVP		0.66
MPC		0.27
ClinPred		0.25	T
GERP RS		3.4
PromoterAI		-0.11	Neutral
Varity_R		0.17
gMVP		0.51
Mutation Taster		=93/7	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: rs926979803; hg19: chr4-144435090;