2-64551634-C-A

Variant names:

• chr2-64551634-C-A
• rs757559539
• NM_203437.4:c.160C>A

Variant summary

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

The NM_203437.4(AFTPH):​c.160C>A​(p.Arg54Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: AFTPH NM_203437.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49
• Publications: 0 publications found

Genes affected

AFTPH (HGNC:25951): (aftiphilin) Enables clathrin binding activity. Predicted to be involved in intracellular transport. Located in Golgi apparatus; cytosol; and nucleoplasm. Part of AP-1 adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC105374773 (HGNC:):

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=0.10887554).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203437.4. 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
	AFTPH	NM_203437.4	MANE Select	c.160C>A	p.Arg54Ser	missense	Exon 2 of 10	NP_982261.2
	AFTPH	NM_001375969.1		c.160C>A	p.Arg54Ser	missense	Exon 2 of 10	NP_001362898.1	A0A8Q3SIA4
	AFTPH	NM_001375970.1		c.160C>A	p.Arg54Ser	missense	Exon 2 of 10	NP_001362899.1	A0A8Q3WM48

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFTPH	ENST00000409933.6	TSL:1 MANE Select	c.160C>A	p.Arg54Ser	missense	Exon 2 of 10	ENSP00000387071.1	Q6ULP2-1
	AFTPH	ENST00000238856.8	TSL:1	c.160C>A	p.Arg54Ser	missense	Exon 2 of 9	ENSP00000238856.4	Q6ULP2-6
	AFTPH	ENST00000498706.5	TSL:1	n.278C>A		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461812 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 727206

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111966

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

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	0.17
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0029	T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.78	N
REVEL	Benign	0.074
Sift	Uncertain	0.016	D
Sift4G	Benign	0.51	T
Polyphen		0.082	B
Vest4		0.19
MutPred		0.18		Gain of phosphorylation at R54 (P = 0.0392)
MVP		0.082
MPC		0.12
ClinPred		0.79	D
GERP RS		4.6
PromoterAI		-0.021	Neutral
Varity_R		0.19
gMVP		0.064
Mutation Taster		=86/14	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: rs757559539; hg19: chr2-64778768;