rs10737190

Variant names:

• chr1-3191932-G-A
• rs10737190
• NM_022114.4:c.387+5458G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-3191932-G-A
• chr1-3191932-G-C
• chr1-3191932-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022114.4(PRDM16):​c.387+5458G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,208 control chromosomes in the GnomAD database, including 61,866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61866 hom., cov: 31)
• Consequence: PRDM16 NM_022114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 4 publications found

Genes affected

PRDM16 (HGNC:14000): (PR/SET domain 16) The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

PRDM16 Gene-Disease associations (from GenCC):

• left ventricular noncompaction 8

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

LOC107984909 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRDM16	NM_022114.4	c.387+5458G>A		intron_variant	Intron 2 of 16	ENST00000270722.10	NP_071397.3
LOC107984909	XR_001737869.2	n.4375G>A		non_coding_transcript_exon_variant	Exon 1 of 2
PRDM16	NM_199454.3	c.387+5458G>A		intron_variant	Intron 2 of 16		NP_955533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRDM16	ENST00000270722.10	c.387+5458G>A		intron_variant	Intron 2 of 16	1	NM_022114.4	ENSP00000270722.5
PRDM16	ENST00000378391.6	c.387+5458G>A		intron_variant	Intron 2 of 16	1		ENSP00000367643.2
PRDM16	ENST00000511072.5	c.387+5458G>A		intron_variant	Intron 2 of 15	5		ENSP00000426975.1
PRDM16	ENST00000514189.5	c.387+5458G>A		intron_variant	Intron 2 of 15	5		ENSP00000421400.1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 137059 AN: 152090 Hom.: 61840 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.900

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.901 AC: 137133 AN: 152208 Hom.: 61866 Cov.: 31 AF XY: 0.901 AC XY: 67044 AN XY: 74416

African (AFR) AF: 0.861 AC: 35734 AN: 41500

American (AMR) AF: 0.908 AC: 13893 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3041 AN: 3468

East Asian (EAS) AF: 0.898 AC: 4628 AN: 5152

South Asian (SAS) AF: 0.846 AC: 4074 AN: 4818

European-Finnish (FIN) AF: 0.952 AC: 10101 AN: 10614

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62675 AN: 68032

Other (OTH) AF: 0.896 AC: 1896 AN: 2116

Alfa AF: 0.913 Hom.: 103793

Bravo AF: 0.897

Asia WGS AF: 0.858 AC: 2982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.47
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10737190; hg19: chr1-3108496; COSMIC: COSV54584337;