chr3-122755330-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024610.6(HSPBAP1):​c.671A>G​(p.Asn224Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000461 in 1,454,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: HSPBAP1 NM_024610.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20476314).

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>G	p.Asn224Ser	missense	Exon 5 of 8	NP_078886.2
	HSPBAP1	NM_001320728.2		c.671A>G	p.Asn224Ser	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>G	p.Asn224Ser	missense	Exon 5 of 8	ENSP00000302562.2	Q96EW2-1
	HSPBAP1	ENST00000467643.5	TSL:1	n.832A>G		non_coding_transcript_exon	Exon 6 of 6
	HSPBAP1	ENST00000936102.1		c.683A>G	p.Asn228Ser	missense	Exon 5 of 8	ENSP00000606161.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 244488 AF XY: 0.0000302

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000269

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.0000461 AC: 67 AN: 1454922 Hom.: 0 Cov.: 31 AF XY: 0.0000359 AC XY: 26 AN XY: 723782

African (AFR) AF: 0.0000304 AC: 1 AN: 32880

American (AMR) AF: 0.00 AC: 0 AN: 43812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25938

East Asian (EAS) AF: 0.00 AC: 0 AN: 39066

South Asian (SAS) AF: 0.00 AC: 0 AN: 85430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.0000532 AC: 59 AN: 1108744

Other (OTH) AF: 0.000117 AC: 7 AN: 60032

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.30	N
PhyloP100		1.9
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.10
Sift	Benign	0.39	T
Sift4G	Benign	0.77	T
Polyphen		0.72	P
Vest4		0.25
MutPred		0.40		Loss of sheet (P = 0.0457)
MVP		0.26
MPC		0.19
ClinPred		0.15	T
GERP RS		5.5
Varity_R		0.16
gMVP		0.34
Mutation Taster		=90/10	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;