HSPA8 p.Phe459Leu

Variant names:

• chr11-123058777-A-T
• NM_006597.6:c.1377T>A
• HSPA8 p.Phe459Leu

Your query was ambiguous. Multiple possible variants found:

• chr11-123058777-A-T
• chr11-123058777-A-C
• chr11-123058779-A-G
• chr11-123058777-AAA-GAG
• chr11-123058777-AAA-TAG
• chr11-123058777-AAA-CAG

Variant summary

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

The NM_006597.6(HSPA8):​c.1377T>A​(p.Phe459Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSPA8 NM_006597.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 0 publications found

Genes affected

HSPA8 (HGNC:5241): (heat shock protein family A (Hsp70) member 8) This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

SNORD14D (HGNC:30353): (small nucleolar RNA, C/D box 14D)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006597.6. 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
	HSPA8	NM_006597.6	MANE Select	c.1377T>A	p.Phe459Leu	missense	Exon 7 of 9	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.1377T>A	p.Phe459Leu	missense	Exon 7 of 8	NP_694881.1	P11142-2
	SNORD14D	NR_001454.2		n.*132T>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.1377T>A	p.Phe459Leu	missense	Exon 7 of 9	ENSP00000432083.1	P11142-1
	HSPA8	ENST00000227378.7	TSL:1	c.1377T>A	p.Phe459Leu	missense	Exon 6 of 8	ENSP00000227378.3	P11142-1
	HSPA8	ENST00000453788.6	TSL:1	c.1377T>A	p.Phe459Leu	missense	Exon 7 of 8	ENSP00000404372.2	P11142-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.1
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.025	D
PromoterAI		-0.0099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.86
Mutation Taster		=28/72	disease causing

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: chr11-122929485;