17-58487959-C-T

Variant names:

• chr17-58487959-C-T
• NM_001080439.3:c.316G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080439.3(HSF5):​c.316G>A​(p.Gly106Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSF5 NM_001080439.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

Genes affected

HSF5 (HGNC:26862): (heat shock transcription factor 5) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24307191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSF5	NM_001080439.3	c.316G>A	p.Gly106Arg	missense_variant	Exon 1 of 6	ENST00000323777.8	NP_001073908.2
HSF5	XM_011524283.2	c.316G>A	p.Gly106Arg	missense_variant	Exon 1 of 6		XP_011522585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSF5	ENST00000323777.8	c.316G>A	p.Gly106Arg	missense_variant	Exon 1 of 6	1	NM_001080439.3	ENSP00000313243.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.316G>A (p.G106R) alteration is located in exon 1 (coding exon 1) of the HSF5 gene. This alteration results from a G to A substitution at nucleotide position 316, causing the glycine (G) at amino acid position 106 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	19
DANN	Benign	0.69
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.56	D
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.43	T
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.23	N
REVEL	Uncertain	0.33
Sift	Benign	0.069	T
Sift4G	Benign	0.13	T
Vest4		0.13
MutPred		0.34		Loss of ubiquitination at K101 (P = 0.0226);
MVP		0.043
MPC		1.9
ClinPred		0.27	T
GERP RS		3.2
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-56565320;