chr14-45196408-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000267430.10(FANCM):āc.5577T>Cā(p.Asn1859=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000589 in 1,614,138 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0029 ( 6 hom., cov: 32)
Exomes š: 0.00035 ( 9 hom. )
Consequence
FANCM
ENST00000267430.10 synonymous
ENST00000267430.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.521
Genes affected
FANCM (HGNC:23168): (FA complementation group M) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group M. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 14-45196408-T-C is Benign according to our data. Variant chr14-45196408-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 241325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.521 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00289 (440/152278) while in subpopulation AFR AF= 0.0103 (426/41558). AF 95% confidence interval is 0.00945. There are 6 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FANCM | NM_020937.4 | c.5577T>C | p.Asn1859= | synonymous_variant | 21/23 | ENST00000267430.10 | NP_065988.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCM | ENST00000267430.10 | c.5577T>C | p.Asn1859= | synonymous_variant | 21/23 | 1 | NM_020937.4 | ENSP00000267430 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00275 AC: 418AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000867 AC: 218AN: 251462Hom.: 1 AF XY: 0.000625 AC XY: 85AN XY: 135904
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GnomAD4 exome AF: 0.000349 AC: 510AN: 1461860Hom.: 9 Cov.: 33 AF XY: 0.000304 AC XY: 221AN XY: 727226
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GnomAD4 genome AF: 0.00289 AC: 440AN: 152278Hom.: 6 Cov.: 32 AF XY: 0.00299 AC XY: 223AN XY: 74466
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 30, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | FANCM: BP4, BS1 - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 07, 2022 | - - |
Premature ovarian failure 15 Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Fanconi anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at