14-102083502-A-T

Variant names:

• chr14-102083502-A-T
• rs7155973
• NM_005348.4:c.1486+44T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005348.4(HSP90AA1):​c.1486+44T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSP90AA1 NM_005348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470
• Publications: 19 publications found

Genes affected

HSP90AA1 (HGNC:5253): (heat shock protein 90 alpha family class A member 1) The protein encoded by this gene is an inducible molecular chaperone that functions as a homodimer. The encoded protein aids in the proper folding of specific target proteins by use of an ATPase activity that is modulated by co-chaperones. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005348.4. 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
	HSP90AA1	NM_005348.4	MANE Select	c.1486+44T>A		intron	N/A	NP_005339.3
	HSP90AA1	NM_001017963.3		c.1852+44T>A		intron	N/A	NP_001017963.2	P07900-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AA1	ENST00000216281.13	TSL:1 MANE Select	c.1486+44T>A		intron	N/A	ENSP00000216281.8	P07900-1
	HSP90AA1	ENST00000334701.11	TSL:1	c.1852+44T>A		intron	N/A	ENSP00000335153.7	P07900-2
	HSP90AA1	ENST00000554401.1	TSL:1	n.*915+44T>A		intron	N/A	ENSP00000451400.1	H0YJF5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1438542 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 717350

African (AFR) AF: 0.00 AC: 0 AN: 32984

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 85720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092986

Other (OTH) AF: 0.00 AC: 0 AN: 59562

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.76
DANN	Benign	0.49
PhyloP100		-0.47

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: rs7155973; hg19: chr14-102549839;