rs777466895

Variant names:

• chr14-77465618-C-A
• rs777466895
• NM_012111.3:c.641C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-77465618-C-A
• chr14-77465618-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012111.3(AHSA1):​c.641C>A​(p.Thr214Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AHSA1 NM_012111.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53
• Publications: 0 publications found

Genes affected

AHSA1 (HGNC:1189): (activator of HSP90 ATPase activity 1) Enables ATPase activator activity; Hsp90 protein binding activity; and chaperone binding activity. Involved in positive regulation of ATPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30953336).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012111.3. 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
	AHSA1	NM_012111.3	MANE Select	c.641C>A	p.Thr214Asn	missense	Exon 6 of 9	NP_036243.1	O95433-1
	AHSA1	NM_001321441.2		c.236C>A	p.Thr79Asn	missense	Exon 6 of 9	NP_001308370.1	G3V438

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHSA1	ENST00000216479.8	TSL:1 MANE Select	c.641C>A	p.Thr214Asn	missense	Exon 6 of 9	ENSP00000216479.3	O95433-1
	AHSA1	ENST00000855622.1		c.641C>A	p.Thr214Asn	missense	Exon 6 of 10	ENSP00000525681.1
	AHSA1	ENST00000920448.1		c.701C>A	p.Thr234Asn	missense	Exon 7 of 10	ENSP00000590507.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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	0.075
PhyloP100		2.5
Varity_R		0.10
gMVP		0.40
Mutation Taster		=55/45	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs777466895; hg19: chr14-77931961; COSMIC: COSV53633008; COSMIC: COSV53633008;