rs556875684
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001371596.2(MFSD8):āc.935T>Cā(p.Ile312Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I312V) has been classified as Uncertain significance.
Frequency
Consequence
NM_001371596.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MFSD8 | NM_001371596.2 | c.935T>C | p.Ile312Thr | missense_variant | 9/12 | ENST00000641686.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MFSD8 | ENST00000641686.2 | c.935T>C | p.Ile312Thr | missense_variant | 9/12 | NM_001371596.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251320Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135828
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461392Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 726982
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74484
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis 7 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics | Apr 17, 2019 | The proband had a homozygous p.Ile312Thr variant in the MFSD8 gene. This variant has been reported in an Indian family with an autosomal recessive inheritance. The proband had abnormal gait, angular vision problem and features suggestive of cerebellar ataxia. MRI showed cerebellar atrophy. The variant has been reported in the dbSNP database with an identification number rs556875684 and in the Exome Aggregation Consortium (ExAC) database, as a rare variant. In-Silico prediction of the variant is damaging by LRT, PolyPhen2 and MutationTaster. In summary, the Ile312Thr variant meets our criteria to be classified as uncertain significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 31, 2015 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.935T>C (p.I312T) alteration is located in exon 10 (coding exon 9) of the MFSD8 gene. This alteration results from a T to C substitution at nucleotide position 935, causing the isoleucine (I) at amino acid position 312 to be replaced by a threonine (T). 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