17-40628942-C-T

Variant names:

• chr17-40628942-C-T
• rs142193069
• NM_003079.5:c.1079G>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003079.5(SMARCE1):​c.1079G>A​(p.Gly360Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00276 in 1,613,810 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G360R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (11 hom.)
• Consequence: SMARCE1 NM_003079.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:6
• Conservation: PhyloP100: 6.82
• Publications: 6 publications found

Genes affected

SMARCE1 (HGNC:11109): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1) The protein encoded by this gene is part of the large ATP-dependent chromatin remodeling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. The encoded protein, either alone or when in the SWI/SNF complex, can bind to 4-way junction DNA, which is thought to mimic the topology of DNA as it enters or exits the nucleosome. The protein contains a DNA-binding HMG domain, but disruption of this domain does not abolish the DNA-binding or nucleosome-displacement activities of the SWI/SNF complex. Unlike most of the SWI/SNF complex proteins, this protein has no yeast counterpart. [provided by RefSeq, Jul 2008]

SMARCE1 Gene-Disease associations (from GenCC):

• familial meningioma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, G2P, Ambry Genetics
• Coffin-Siris syndrome 5

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Coffin-Siris syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial multiple meningioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000264058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013834089).
• BP6: Variant 17-40628942-C-T is Benign according to our data. Variant chr17-40628942-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 239487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 214 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003079.5. 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
	SMARCE1	NM_003079.5	MANE Select	c.1079G>A	p.Gly360Asp	missense	Exon 11 of 11	NP_003070.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMARCE1	ENST00000348513.12	TSL:1 MANE Select	c.1079G>A	p.Gly360Asp	missense	Exon 11 of 11	ENSP00000323967.6
	SMARCE1	ENST00000578044.6	TSL:1	c.869G>A	p.Gly290Asp	missense	Exon 8 of 8	ENSP00000464511.1
	SMARCE1	ENST00000377808.9	TSL:1	c.*66G>A		3_prime_UTR	Exon 11 of 11	ENSP00000367039.4

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 214 AN: 152116 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00147 AC: 368 AN: 251080 AF XY: 0.00157

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00260

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00290 AC: 4241 AN: 1461576 Hom.: 11 Cov.: 31 AF XY: 0.00274 AC XY: 1995 AN XY: 727104

African (AFR) AF: 0.000448 AC: 15 AN: 33470

American (AMR) AF: 0.000470 AC: 21 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00148 AC: 128 AN: 86250

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53376

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.00354 AC: 3936 AN: 1111796

Other (OTH) AF: 0.00204 AC: 123 AN: 60378

GnomAD4 genome AF: 0.00141 AC: 214 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.00132 AC XY: 98 AN XY: 74432

African (AFR) AF: 0.000361 AC: 15 AN: 41538

American (AMR) AF: 0.000653 AC: 10 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00268 AC: 182 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00176 Hom.: 0

Bravo AF: 0.00148

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00209 AC: 18

ExAC AF: 0.00143 AC: 174

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00213

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	2	not provided (3)
-	-	1	Familial meningioma (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	not specified (1)
-	-	1	SMARCE1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		6.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.20
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.52	T
Polyphen		1.0	D
Vest4		0.58
MVP		0.27
MPC		1.7
ClinPred		0.024	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.049
Mutation Taster		=88/12	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: rs142193069; hg19: chr17-38785194; COSMIC: COSV99228553; COSMIC: COSV99228553;