11-65779292-G-A

Variant names:

• chr11-65779292-G-A
• rs201041158
• NM_138368.5:c.1201C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_138368.5(AP5B1):​c.1201C>T​(p.Leu401Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,599,532 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (15 hom.)
• Consequence: AP5B1 NM_138368.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 2.81
• Publications: 6 publications found

Genes affected

AP5B1 (HGNC:25104): (adaptor related protein complex 5 subunit beta 1) Involved in endosomal transport. Located in lysosomal membrane. Part of AP-type membrane coat adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009311676).
• BS2: High Homozygotes in GnomAdExome4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138368.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP5B1	NM_138368.5	MANE Select	c.1201C>T	p.Leu401Phe	missense	Exon 2 of 2	NP_612377.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP5B1	ENST00000532090.3	TSL:1 MANE Select	c.1201C>T	p.Leu401Phe	missense	Exon 2 of 2	ENSP00000454303.1

Frequencies

GnomAD3 genomes AF: 0.00313 AC: 476 AN: 152242 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00541

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00310 AC: 726 AN: 234356 AF XY: 0.00304

Gnomad AFR exome AF: 0.000466

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00128

Gnomad NFE exome AF: 0.00529

Gnomad OTH exome AF: 0.00388

GnomAD4 exome AF: 0.00432 AC: 6256 AN: 1447172 Hom.: 15 Cov.: 30 AF XY: 0.00418 AC XY: 3002 AN XY: 718470

African (AFR) AF: 0.000692 AC: 23 AN: 33250

American (AMR) AF: 0.00248 AC: 108 AN: 43626

Ashkenazi Jewish (ASJ) AF: 0.000918 AC: 23 AN: 25044

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39560

South Asian (SAS) AF: 0.000997 AC: 84 AN: 84220

European-Finnish (FIN) AF: 0.00157 AC: 81 AN: 51664

Middle Eastern (MID) AF: 0.00158 AC: 9 AN: 5698

European-Non Finnish (NFE) AF: 0.00517 AC: 5705 AN: 1104362

Other (OTH) AF: 0.00372 AC: 222 AN: 59748

GnomAD4 genome AF: 0.00312 AC: 476 AN: 152360 Hom.: 1 Cov.: 33 AF XY: 0.00294 AC XY: 219 AN XY: 74508

African (AFR) AF: 0.000649 AC: 27 AN: 41582

American (AMR) AF: 0.00300 AC: 46 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4832

European-Finnish (FIN) AF: 0.00169 AC: 18 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00541 AC: 368 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00474 Hom.: 6

Bravo AF: 0.00322

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.000956 AC: 4

ESP6500EA AF: 0.00499 AC: 42

ExAC AF: 0.00344 AC: 415

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Aug 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1030C>T (p.L344F) alteration is located in exon 1 (coding exon 1) of the AP5B1 gene. This alteration results from a C to T substitution at nucleotide position 1030, causing the leucine (L) at amino acid position 344 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Hereditary spastic paraplegia Uncertain:1

Mar 07, 2017

Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

not provided Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0086	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.75	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.0093	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		2.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.32	N
Sift	Benign	0.21	T
Sift4G	Pathogenic	0.0	D
Vest4		0.50
MVP		0.60
MPC		0.41
GERP RS		5.0
Varity_R		0.064
gMVP		0.45
Mutation Taster		=92/8	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

dbSNP: rs201041158; hg19: chr11-65546763; COSMIC: COSV57503167;