AMPH p.Ala494Ala

Variant names:

• chr7-38394130-C-C
• NM_001635.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr7-38394131--
• chr7-38394131-C-A
• chr7-38394131-C-G
• chr7-38394131-C-T

Variant summary

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

The NM_001635.4(AMPH):​c. variant causes a exon region 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMPH NM_001635.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541
• Publications: 0 publications found

Genes affected

AMPH (HGNC:471): (amphiphysin) This gene encodes a protein associated with the cytoplasmic surface of synaptic vesicles. A subset of patients with stiff-man syndrome who were also affected by breast cancer are positive for autoantibodies against this protein. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional splice variants have been described, but their full length sequences have not been determined. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Nov 2010]

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_001635.4. 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
	AMPH	NM_001635.4	MANE Select	c.		exon_region	Exon 18 of 21	NP_001626.1	P49418-1
	AMPH	NM_139316.3		c.		exon_region	Exon 17 of 20	NP_647477.1	P49418-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPH	ENST00000356264.7	TSL:1 MANE Select	c.		exon_region	Exon 18 of 21	ENSP00000348602.2	P49418-1
	AMPH	ENST00000325590.9	TSL:1	c.		exon_region	Exon 17 of 20	ENSP00000317441.5	P49418-2
	AMPH	ENST00000441628.5	TSL:1	c.		exon_region	Exon 9 of 12	ENSP00000415085.1	H0Y7T8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.54

Splicing

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

hg19: chr7-38433730;