8-105419242-T-A
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_012082.4(ZFPM2):c.139T>A(p.Ser47Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_012082.4 missense
Scores
Clinical Significance
Conservation
Publications
- 46,XY sex reversal 9Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- diaphragmatic hernia 3Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
- tetralogy of fallotInheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- 46,XY partial gonadal dysgenesisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000402 AC: 1AN: 248974 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461428Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726994 show subpopulations
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74308 show subpopulations
ClinVar
Submissions by phenotype
46,XY sex reversal 9 Uncertain:1
This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 47 of the ZFPM2 protein (p.Ser47Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZFPM2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at