3-122755330-T-A

Variant names:

• chr3-122755330-T-A
• rs768054812
• NM_024610.6:c.671A>T

Variant summary

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

The NM_024610.6(HSPBAP1):​c.671A>T​(p.Asn224Ile) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N224S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: HSPBAP1 NM_024610.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 0 publications found

Genes affected

HSPBAP1 (HGNC:16389): (HSPB1 associated protein 1) This gene encodes a protein that binds to one of the small heat shock proteins, specifically hsp27. Hsp27 is involved with cell growth and differentiation. This encoded protein was found to be abnormally expressed in patients with intractable epilepsy, although how brain function is affected remains unknown. [provided by RefSeq, Sep 2011]

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_024610.6. 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
	HSPBAP1	NM_024610.6	MANE Select	c.671A>T	p.Asn224Ile	missense	Exon 5 of 8	NP_078886.2
	HSPBAP1	NM_001320728.2		c.671A>T	p.Asn224Ile	missense	Exon 5 of 7	NP_001307657.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPBAP1	ENST00000306103.3	TSL:1 MANE Select	c.671A>T	p.Asn224Ile	missense	Exon 5 of 8	ENSP00000302562.2	Q96EW2-1
	HSPBAP1	ENST00000467643.5	TSL:1	n.832A>T		non_coding_transcript_exon	Exon 6 of 6
	HSPBAP1	ENST00000936102.1		c.683A>T	p.Asn228Ile	missense	Exon 5 of 8	ENSP00000606161.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244488 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000569

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.9
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.46		Gain of methylation at K228 (P = 0.0367)
MVP		0.46
MPC		0.85
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.63
gMVP		0.62
Mutation Taster		=72/28	polymorphism

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: rs768054812; hg19: chr3-122474177;