chr18-2656122-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBS1_SupportingBS2
The NM_015295.3(SMCHD1):āc.47C>Gā(p.Thr16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000473 in 1,478,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T16I) has been classified as Uncertain significance.
Frequency
Consequence
NM_015295.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMCHD1 | NM_015295.3 | c.47C>G | p.Thr16Ser | missense_variant | 1/48 | ENST00000320876.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMCHD1 | ENST00000320876.11 | c.47C>G | p.Thr16Ser | missense_variant | 1/48 | 5 | NM_015295.3 | P2 | |
SMCHD1 | ENST00000688342.1 | c.47C>G | p.Thr16Ser | missense_variant | 1/47 | A2 | |||
SMCHD1 | ENST00000684915.1 | n.204C>G | non_coding_transcript_exon_variant | 1/14 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000363 AC: 5AN: 137766Hom.: 0 AF XY: 0.0000259 AC XY: 2AN XY: 77274
GnomAD4 exome AF: 0.0000475 AC: 63AN: 1326748Hom.: 0 Cov.: 29 AF XY: 0.0000412 AC XY: 27AN XY: 655590
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74420
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 07, 2023 | The c.47C>G (p.T16S) alteration is located in exon 1 (coding exon 1) of the SMCHD1 gene. This alteration results from a C to G substitution at nucleotide position 47, causing the threonine (T) at amino acid position 16 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at