16-50073472-T-C

Position:

• chr16-50073472-T-C

Variant summary

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

The NM_182922.4(HEATR3):​c.622+758T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 152,250 control chromosomes in the GnomAD database, including 63,062 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 0.91 (63062 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HEATR3 NM_182922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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]

ENSG00000279356 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEATR3	NM_182922.4	c.622+758T>C		intron_variant		ENST00000299192.8	NP_891552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEATR3	ENST00000299192.8	c.622+758T>C		intron_variant		1	NM_182922.4	ENSP00000299192.7

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138342 AN: 152132 Hom.: 63015 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.954

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.913

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.909 AC: 138450 AN: 152250 Hom.: 63062 Cov.: 32 AF XY: 0.910 AC XY: 67712 AN XY: 74432

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.901

Gnomad4 ASJ AF: 0.955

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.954

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.912

Alfa AF: 0.919 Hom.: 39011

Bravo AF: 0.901

Asia WGS AF: 0.838 AC: 2916 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	4.1
DANN	Benign	0.62

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: rs1861662; hg19: chr16-50107383;