rs775817223

Variant names:

• chr17-58458905-T-C
• rs775817223
• NM_001080439.3:c.1583A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-58458905-T-C
• chr17-58458905-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080439.3(HSF5):​c.1583A>G​(p.Asn528Ser) 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. 13/19 in silico tools predict a benign 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. N528T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HSF5 NM_001080439.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051811874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSF5	NM_001080439.3	c.1583A>G	p.Asn528Ser	missense_variant	Exon 5 of 6	ENST00000323777.8	NP_001073908.2
HSF5	XM_011524283.2	c.1604A>G	p.Asn535Ser	missense_variant	Exon 5 of 6		XP_011522585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSF5	ENST00000323777.8	c.1583A>G	p.Asn528Ser	missense_variant	Exon 5 of 6	1	NM_001080439.3	ENSP00000313243.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Uncertain	0.98
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.66	D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.97	T
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.067
Sift	Benign	0.17	T
Sift4G	Benign	0.11	T
Vest4		0.10
MutPred		0.19		Gain of phosphorylation at N528 (P = 0.0184);
MVP		0.068
MPC		0.16
ClinPred		0.13	T
GERP RS		2.0
gMVP		0.063

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs775817223; hg19: chr17-56536266;