chr16-50066204-G-C

Variant names:

• chr16-50066204-G-C
• NM_182922.4:c.73G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182922.4(HEATR3):​c.73G>C​(p.Ala25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEATR3 NM_182922.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.959
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24352747).

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.73G>C	p.Ala25Pro	missense	Exon 1 of 15	NP_891552.1	Q7Z4Q2-1
	HEATR3	NM_001329729.2		c.-620G>C		5_prime_UTR	Exon 1 of 16	NP_001316658.1
	HEATR3	NM_001329730.2		c.-594G>C		5_prime_UTR	Exon 1 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.73G>C	p.Ala25Pro	missense	Exon 1 of 15	ENSP00000299192.7	Q7Z4Q2-1
	HEATR3	ENST00000887924.1		c.73G>C	p.Ala25Pro	missense	Exon 1 of 15	ENSP00000557983.1
	HEATR3	ENST00000887923.1		c.73G>C	p.Ala25Pro	missense	Exon 1 of 14	ENSP00000557982.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.12
PhyloP100		0.96
PromoterAI		-0.044	Neutral
Varity_R		0.33
gMVP		0.42

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-50100115;