18-2739450-T-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The ENST00000320876.11(SMCHD1):c.3444T>C(p.Pro1148Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,986 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. Synonymous variant affecting the same amino acid position (i.e. P1148P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SMCHD1
ENST00000320876.11 synonymous
ENST00000320876.11 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.360
Publications
4 publications found
Genes affected
SMCHD1 (HGNC:29090): (structural maintenance of chromosomes flexible hinge domain containing 1) This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family. [provided by RefSeq, Dec 2011]
SMCHD1 Gene-Disease associations (from GenCC):
- arhinia, choanal atresia, and microphthalmiaInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, ClinGen, Illumina
- facioscapulohumeral muscular dystrophyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndromeInheritance: 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 -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP7
Synonymous conserved (PhyloP=0.36 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000320876.11. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SMCHD1 | NM_015295.3 | MANE Select | c.3444T>C | p.Pro1148Pro | synonymous | Exon 27 of 48 | NP_056110.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SMCHD1 | ENST00000320876.11 | TSL:5 MANE Select | c.3444T>C | p.Pro1148Pro | synonymous | Exon 27 of 48 | ENSP00000326603.7 | ||
| SMCHD1 | ENST00000688342.1 | c.3444T>C | p.Pro1148Pro | synonymous | Exon 27 of 47 | ENSP00000508422.1 | |||
| SMCHD1 | ENST00000577880.5 | TSL:2 | n.1857T>C | non_coding_transcript_exon | Exon 16 of 38 | ENSP00000463049.1 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152128
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
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AF:
Gnomad FIN
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.00000402 AC: 1AN: 248542 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
248542
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460858Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726742 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460858
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
726742
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33416
American (AMR)
AF:
AC:
0
AN:
44638
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26104
East Asian (EAS)
AF:
AC:
0
AN:
39582
South Asian (SAS)
AF:
AC:
0
AN:
86244
European-Finnish (FIN)
AF:
AC:
0
AN:
53394
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111398
Other (OTH)
AF:
AC:
0
AN:
60324
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
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0.60
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152128
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74316
show subpopulations
African (AFR)
AF:
AC:
2
AN:
41420
American (AMR)
AF:
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5198
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10604
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68014
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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