NM_182922.4:c.236A>G

Variant names:

• chr16-50066464-A-G
• rs1247944572
• NM_182922.4:c.236A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182922.4(HEATR3):​c.236A>G​(p.Asp79Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000022 in 1,360,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: HEATR3 NM_182922.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28
• Publications: 1 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-AS1 (HGNC:55406): (HEATR3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182922.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR3	NM_182922.4	MANE Select	c.236A>G	p.Asp79Gly	missense	Exon 2 of 15	NP_891552.1	Q7Z4Q2-1
	HEATR3	NM_001329729.2		c.-457A>G		5_prime_UTR	Exon 2 of 16	NP_001316658.1
	HEATR3	NM_001329730.2		c.-431A>G		5_prime_UTR	Exon 2 of 16	NP_001316659.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR3	ENST00000299192.8	TSL:1 MANE Select	c.236A>G	p.Asp79Gly	missense	Exon 2 of 15	ENSP00000299192.7	Q7Z4Q2-1
	HEATR3	ENST00000887924.1		c.236A>G	p.Asp79Gly	missense	Exon 2 of 15	ENSP00000557983.1
	HEATR3	ENST00000887923.1		c.236A>G	p.Asp79Gly	missense	Exon 2 of 14	ENSP00000557982.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151968 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000442

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000223 AC: 27 AN: 1208880 Hom.: 0 Cov.: 33 AF XY: 0.0000188 AC XY: 11 AN XY: 586030

African (AFR) AF: 0.00 AC: 0 AN: 23948

American (AMR) AF: 0.00 AC: 0 AN: 9608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16780

East Asian (EAS) AF: 0.0000364 AC: 1 AN: 27446

South Asian (SAS) AF: 0.00 AC: 0 AN: 51378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4570

European-Non Finnish (NFE) AF: 0.0000261 AC: 26 AN: 996398

Other (OTH) AF: 0.00 AC: 0 AN: 49740

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151968 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74226

African (AFR) AF: 0.00 AC: 0 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000442 AC: 3 AN: 67934

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.034
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.3
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.22
Sift	Benign	0.035	D
Sift4G	Benign	0.076	T
Polyphen		0.64	P
Vest4		0.49
MutPred		0.46		Gain of MoRF binding (P = 0.0337)
MVP		0.75
MPC		0.49
ClinPred		0.88	D
GERP RS		3.4
PromoterAI		-0.0051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.18
gMVP		0.63
Mutation Taster		=84/16	polymorphism

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: rs1247944572; hg19: chr16-50100375;