NM_022114.4:c.3301G>A
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_022114.4(PRDM16):c.3301G>A(p.Val1101Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,614,114 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_022114.4 missense
Scores
Clinical Significance
Conservation
Publications
- left ventricular noncompaction 8Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- left ventricular noncompactionInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- dilated cardiomyopathyInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000788 AC: 120AN: 152224Hom.: 3 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.00317 AC: 785AN: 247326 AF XY: 0.00426 show subpopulations
GnomAD4 exome AF: 0.00157 AC: 2288AN: 1461772Hom.: 43 Cov.: 32 AF XY: 0.00222 AC XY: 1612AN XY: 727178 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.000794 AC: 121AN: 152342Hom.: 3 Cov.: 33 AF XY: 0.00122 AC XY: 91AN XY: 74494 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Benign:3
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p.Val1101Met in exon 15 of PRDM16: This variant is not expected to have clinical significance because it has been identified in 2.6% (422/16468) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs201654872). -
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not provided Benign:3
PRDM16: BP4, BS1, BS2 -
This variant is associated with the following publications: (PMID: 27896284, 27535533, 24387995, 23768516) -
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Left ventricular noncompaction 8 Benign:2
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The heterozygous p.Val1101Met variant in PRDM16 has been identified in 2 individuals with dilated cardiomyopathy (PMID: 23768516), and has been identified in >2% of South Asian chromosomes and 7 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal dominant dilated cardiomyopathy. -
Cardiomyopathy, dilated, 1LL Uncertain:1
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PRDM16-related disorder Benign:1
This variant is classified as 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