14-57274542-G-A

Position:

• chr14-57274542-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000261558.8(AP5M1):​c.373G>A​(p.Val125Ile) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP5M1 ENST00000261558.8 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

Genes affected

AP5M1 (HGNC:20192): (adaptor related protein complex 5 subunit mu 1) Involved in endosomal transport. Located in several cellular components, including cytosol; late endosome; and lysosome. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

AP5M1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030474454).
• BP6: Variant 14-57274542-G-A is Benign according to our data. Variant chr14-57274542-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2299840.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP5M1	NM_018229.4	c.373G>A	p.Val125Ile	missense_variant	2/8	ENST00000261558.8	NP_060699.3
AP5M1	XM_011536940.4	c.415G>A	p.Val139Ile	missense_variant	3/9		XP_011535242.1
AP5M1	NR_026895.2	n.418+5154G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP5M1	ENST00000261558.8	c.373G>A	p.Val125Ile	missense_variant	2/8	1	NM_018229.4	ENSP00000261558.3
AP5M1	ENST00000431972.6	c.415G>A	p.Val139Ile	missense_variant	3/9	2		ENSP00000390531.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.7
DANN	Benign	0.58
DEOGEN2	Benign	0.00035	T;T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.030	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.3	N;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.52	N;N;N
REVEL	Benign	0.072
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.080
MutPred		0.35		Gain of sheet (P = 4e-04);.;.;
MVP		0.26
MPC		0.089
ClinPred		0.046	T
GERP RS		3.5
Varity_R		0.018
gMVP		0.23

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-57741260;