NM_001635.4:c.1580C>G

Variant names:

• chr7-38394033-G-C
• NM_001635.4:c.1580C>G

Variant summary

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

The NM_001635.4(AMPH):​c.1580C>G​(p.Ala527Gly) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AMPH NM_001635.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076473445).

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.1580C>G	p.Ala527Gly	missense	Exon 18 of 21	NP_001626.1	P49418-1
	AMPH	NM_139316.3		c.1454C>G	p.Ala485Gly	missense	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.1580C>G	p.Ala527Gly	missense	Exon 18 of 21	ENSP00000348602.2	P49418-1
	AMPH	ENST00000325590.9	TSL:1	c.1454C>G	p.Ala485Gly	missense	Exon 17 of 20	ENSP00000317441.5	P49418-2
	AMPH	ENST00000441628.5	TSL:1	c.1226C>G	p.Ala409Gly	missense	Exon 9 of 12	ENSP00000415085.1	H0Y7T8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.074
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.7
DANN	Benign	0.33
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.2
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.066
Sift	Benign	0.44	T
Sift4G	Benign	0.36	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.16		Loss of glycosylation at S522 (P = 0.1456)
MVP		0.83
MPC		0.19
ClinPred		0.070	T
GERP RS		4.1
Varity_R		0.029
gMVP		0.083
Mutation Taster		=97/3	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

hg19: chr7-38433633;