chr10-127175735-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001039762.3(INSYN2A):c.661G>A(p.Asp221Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,614,078 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D221Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_001039762.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INSYN2A | NM_001039762.3 | c.661G>A | p.Asp221Asn | missense_variant | 4/6 | ENST00000522781.6 | |
DOCK1 | NM_001290223.2 | c.2847+47971C>T | intron_variant | ENST00000623213.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INSYN2A | ENST00000522781.6 | c.661G>A | p.Asp221Asn | missense_variant | 4/6 | 2 | NM_001039762.3 | P1 | |
DOCK1 | ENST00000623213.2 | c.2847+47971C>T | intron_variant | 1 | NM_001290223.2 |
Frequencies
GnomAD3 genomes ? AF: 0.000316 AC: 48AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000168 AC: 42AN: 250380Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135652
GnomAD4 exome AF: 0.000101 AC: 147AN: 1461822Hom.: 1 Cov.: 31 AF XY: 0.000107 AC XY: 78AN XY: 727214
GnomAD4 genome ? AF: 0.000309 AC: 47AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74450
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 22, 2021 | The c.661G>A (p.D221N) alteration is located in exon 4 (coding exon 1) of the FAM196A gene. This alteration results from a G to A substitution at nucleotide position 661, causing the aspartic acid (D) at amino acid position 221 to be replaced by an asparagine (N). 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