16-50073472-T-C

Variant names:

• chr16-50073472-T-C
• rs1861662
• NM_182922.4:c.622+758T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

HEATR3 Gene-Disease associations (from GenCC):

• Diamond-Blackfan anemia 21

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000279356 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HEATR3	NM_182922.4	c.622+758T>C		intron_variant	Intron 5 of 14	ENST00000299192.8	NP_891552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR3	ENST00000299192.8	c.622+758T>C		intron_variant	Intron 5 of 14	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.898 AC: 37291 AN: 41542

American (AMR) AF: 0.901 AC: 13786 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3315 AN: 3470

East Asian (EAS) AF: 0.742 AC: 3842 AN: 5178

South Asian (SAS) AF: 0.902 AC: 4346 AN: 4818

European-Finnish (FIN) AF: 0.954 AC: 10118 AN: 10604

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62676 AN: 68024

Other (OTH) AF: 0.912 AC: 1928 AN: 2114

Alfa AF: 0.917 Hom.: 47357

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
PhyloP100		-0.10
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: rs1861662; hg19: chr16-50107383;