GeneBe

4-94226402-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020159.5(SMARCAD1):​c.368+106C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000292 in 342,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 18)
Exomes 𝑓: 0.0000029 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SMARCAD1
NM_020159.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

0 publications found
Variant links:
Genes affected
SMARCAD1 (HGNC:18398): (SWI/SNF-related, matrix-associated actin-dependent regulator of chromatin, subfamily a, containing DEAD/H box 1) This gene encodes a member of the SNF subfamily of helicase proteins. The encoded protein plays a critical role in the restoration of heterochromatin organization and propagation of epigenetic patterns following DNA replication by mediating histone H3/H4 deacetylation. Mutations in this gene are associated with adermatoglyphia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
SMARCAD1 Gene-Disease associations (from GenCC):
  • ectodermal dysplasia syndrome
    Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina
  • isolated congenital adermatoglyphia
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
  • palmoplantar keratoderma-sclerodactyly syndrome
    Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P
  • absence of fingerprints-congenital milia syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SMARCAD1
NM_020159.5
MANE Select
c.368+106C>A
intron
N/ANP_064544.2Q9H4L7-1
SMARCAD1
NM_001128429.3
c.368+106C>A
intron
N/ANP_001121901.1Q9H4L7-2
SMARCAD1
NM_001128430.2
c.368+106C>A
intron
N/ANP_001121902.1Q9H4L7-2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
SMARCAD1
ENST00000354268.9
TSL:1 MANE Select
c.368+106C>A
intron
N/AENSP00000346217.4Q9H4L7-1
SMARCAD1
ENST00000359052.8
TSL:1
c.368+106C>A
intron
N/AENSP00000351947.4Q9H4L7-2
SMARCAD1
ENST00000457823.6
TSL:1
c.368+106C>A
intron
N/AENSP00000415576.2Q9H4L7-2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
124022
Hom.:
0
Cov.:
18
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000292
AC:
1
AN:
342116
Hom.:
0
AF XY:
0.00000545
AC XY:
1
AN XY:
183378
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
8428
American (AMR)
AF:
0.00
AC:
0
AN:
11970
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
9720
East Asian (EAS)
AF:
0.00
AC:
0
AN:
20248
South Asian (SAS)
AF:
0.00
AC:
0
AN:
32070
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
20974
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1310
European-Non Finnish (NFE)
AF:
0.00000456
AC:
1
AN:
219538
Other (OTH)
AF:
0.00
AC:
0
AN:
17858
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
124024
Hom.:
0
Cov.:
18
AF XY:
0.00
AC XY:
0
AN XY:
58044
African (AFR)
AF:
0.00
AC:
0
AN:
32570
American (AMR)
AF:
0.00
AC:
0
AN:
11286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3224
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4458
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4056
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
4082
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
202
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
61614
Other (OTH)
AF:
0.00
AC:
0
AN:
1696

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.14
DANN
Benign
0.29
PhyloP100
-1.3

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

Other links and lift over

dbSNP: rs72665660; hg19: chr4-95147553; API