17-60046222-C-A

Variant names:

• chr17-60046222-C-A
• rs200308045
• NM_022070.5:c.2777G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_022070.5(HEATR6):​c.2777G>T​(p.Ser926Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S926N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEATR6 NM_022070.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92
• Publications: 0 publications found

Genes affected

HEATR6 (HGNC:24076): (HEAT repeat containing 6) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.86

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022070.5. 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
	HEATR6	NM_022070.5	MANE Select	c.2777G>T	p.Ser926Ile	missense	Exon 19 of 20	NP_071353.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HEATR6	ENST00000184956.11	TSL:1 MANE Select	c.2777G>T	p.Ser926Ile	missense	Exon 19 of 20	ENSP00000184956.5	Q6AI08
	HEATR6	ENST00000587003.5	TSL:1	n.*1548G>T		non_coding_transcript_exon	Exon 19 of 20	ENSP00000466192.1	K7ELR8
	HEATR6	ENST00000587003.5	TSL:1	n.*1548G>T		3_prime_UTR	Exon 19 of 20	ENSP00000466192.1	K7ELR8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		4.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.47
Sift	Benign	0.24	T
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.57		Loss of helix (P = 0.0093)
MVP		0.82
MPC		0.55
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.55
gMVP		0.59

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: rs200308045; hg19: chr17-58123583;