3-47590670-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003074.4(SMARCC1):​c.3211A>G​(p.Asn1071Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000467 in 1,542,432 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 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

SMARCC1
NM_003074.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.36
Variant links:
Genes affected
SMARCC1 (HGNC:11104): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 1) The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and contains a predicted leucine zipper motif typical of many transcription factors. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.22027624).
BS2
High AC in GnomAd4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMARCC1NM_003074.4 linkc.3211A>G p.Asn1071Asp missense_variant Exon 27 of 28 ENST00000254480.10 NP_003065.3 Q92922Q58EY4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMARCC1ENST00000254480.10 linkc.3211A>G p.Asn1071Asp missense_variant Exon 27 of 28 1 NM_003074.4 ENSP00000254480.5 Q92922
SMARCC1ENST00000425518.5 linkn.3101A>G non_coding_transcript_exon_variant Exon 27 of 28 2
SMARCC1ENST00000492896.1 linkn.*136A>G downstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000459
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.0000568
AC:
11
AN:
193500
Hom.:
0
AF XY:
0.0000660
AC XY:
7
AN XY:
106062
show subpopulations
Gnomad AFR exome
AF:
0.000574
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000929
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000229
GnomAD4 exome
AF:
0.0000360
AC:
50
AN:
1390176
Hom.:
0
Cov.:
30
AF XY:
0.0000421
AC XY:
29
AN XY:
688608
show subpopulations
Gnomad4 AFR exome
AF:
0.000845
Gnomad4 AMR exome
AF:
0.0000702
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000133
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000209
GnomAD4 genome
AF:
0.000144
AC:
22
AN:
152256
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.000457
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.0243
Hom.:
2354
Bravo
AF:
0.000264
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Nov 12, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3211A>G (p.N1071D) alteration is located in exon 27 (coding exon 27) of the SMARCC1 gene. This alteration results from a A to G substitution at nucleotide position 3211, causing the asparagine (N) at amino acid position 1071 to be replaced by an aspartic acid (D). 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
Uncertain
0.40
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.094
Sift
Benign
0.037
D
Sift4G
Benign
0.63
T
Polyphen
0.96
P
Vest4
0.61
MVP
0.60
MPC
0.33
ClinPred
0.081
T
GERP RS
5.5
Varity_R
0.13
gMVP
0.044

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: rs139202319; hg19: chr3-47632160; API