14-77468469-C-G

Variant names:

• chr14-77468469-C-G
• rs934661331
• NM_012111.3:c.805C>G

Variant summary

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

The NM_012111.3(AHSA1):​c.805C>G​(p.His269Asp) 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. 14/21 in silico tools predict a benign outcome for this variant. 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. H269Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: AHSA1 NM_012111.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25815082).

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.805C>G	p.His269Asp	missense	Exon 8 of 9	NP_036243.1	O95433-1
	AHSA1	NM_001321441.2		c.400C>G	p.His134Asp	missense	Exon 8 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.805C>G	p.His269Asp	missense	Exon 8 of 9	ENSP00000216479.3	O95433-1
	AHSA1	ENST00000855622.1		c.805C>G	p.His269Asp	missense	Exon 8 of 10	ENSP00000525681.1
	AHSA1	ENST00000920448.1		c.865C>G	p.His289Asp	missense	Exon 9 of 10	ENSP00000590507.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.0014	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.8
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.072
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.022	D
Polyphen		0.0040	B
Vest4		0.49
MutPred		0.56		Loss of sheet (P = 0.0126)
MVP		0.44
MPC		1.1
ClinPred		0.85	D
GERP RS		3.4
Varity_R		0.28
gMVP		0.69
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs934661331; hg19: chr14-77934812;