rs4785204

Positions:

• chr16-50069823-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182922.4(HEATR3):​c.400-355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,174 control chromosomes in the GnomAD database, including 687 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 0.088 (687 hom., cov: 32)
• Consequence: HEATR3 NM_182922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

Genes affected

HEATR3 (HGNC:26087): (HEAT repeat containing 3) The protein encoded by this gene plays a role in ribosomal protein transport and in the assembly of the 5S ribonucleoprotein particle (5S RNP). The encoded protein also may be involved in NOD2-mediated NF-kappaB signaling. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEATR3	NM_182922.4	c.400-355C>T		intron_variant		ENST00000299192.8	NP_891552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEATR3	ENST00000299192.8	c.400-355C>T		intron_variant		1	NM_182922.4	ENSP00000299192.7

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13416 AN: 152056 Hom.: 690 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0978

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0835

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

GnomAD4 genome AF: 0.0882 AC: 13423 AN: 152174 Hom.: 687 Cov.: 32 AF XY: 0.0879 AC XY: 6538 AN XY: 74404

Gnomad4 AFR AF: 0.0940

Gnomad4 AMR AF: 0.0979

Gnomad4 ASJ AF: 0.0446

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.0975

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0786

Gnomad4 OTH AF: 0.0850

Alfa AF: 0.0797 Hom.: 151

Bravo AF: 0.0959

Asia WGS AF: 0.157 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs4785204; hg19: chr16-50103734;