rs76935412
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP3BP4_ModerateBP6BS2
The NM_002250.3(KCNN4):c.1018C>A(p.His340Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,614,232 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002250.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNN4 | NM_002250.3 | c.1018C>A | p.His340Asn | missense_variant | Exon 6 of 9 | ENST00000648319.1 | NP_002241.1 | |
KCNN4 | XM_005258882.3 | c.922C>A | p.His308Asn | missense_variant | Exon 5 of 8 | XP_005258939.1 | ||
KCNN4 | XM_005258883.3 | c.829C>A | p.His277Asn | missense_variant | Exon 6 of 9 | XP_005258940.1 | ||
KCNN4 | XM_047438794.1 | c.346C>A | p.His116Asn | missense_variant | Exon 4 of 7 | XP_047294750.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000965 AC: 147AN: 152254Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00154 AC: 387AN: 251420Hom.: 0 AF XY: 0.00148 AC XY: 201AN XY: 135888
GnomAD4 exome AF: 0.00122 AC: 1781AN: 1461860Hom.: 4 Cov.: 32 AF XY: 0.00125 AC XY: 910AN XY: 727242
GnomAD4 genome AF: 0.000958 AC: 146AN: 152372Hom.: 0 Cov.: 32 AF XY: 0.000859 AC XY: 64AN XY: 74506
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
PP3, PS3 -
- -
Reported in two probands with clinical suspicion of hereditary erythrocyte defects, but parental segregation information was not provided and both individuals were reported to have potentially causative variants in other genes as well (Andolfo et al., 2021); Reported in an individual with transient anemia in infancy, but the variant was inherited from an asymptomatic mother (Allegrini et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34201899, 36003639) -
KCNN4-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at