chr2-64551584-T-C

Variant names:

• chr2-64551584-T-C
• NM_203437.4:c.110T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_203437.4(AFTPH):​c.110T>C​(p.Val37Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AFTPH NM_203437.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34839267).

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.110T>C	p.Val37Ala	missense	Exon 2 of 10	NP_982261.2
	AFTPH	NM_001375969.1		c.110T>C	p.Val37Ala	missense	Exon 2 of 10	NP_001362898.1	A0A8Q3SIA4
	AFTPH	NM_001375970.1		c.110T>C	p.Val37Ala	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.110T>C	p.Val37Ala	missense	Exon 2 of 10	ENSP00000387071.1	Q6ULP2-1
	AFTPH	ENST00000238856.8	TSL:1	c.110T>C	p.Val37Ala	missense	Exon 2 of 9	ENSP00000238856.4	Q6ULP2-6
	AFTPH	ENST00000498706.5	TSL:1	n.228T>C		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	0.31
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.093
Sift	Benign	0.10	T
Sift4G	Benign	0.10	T
Polyphen		0.49	P
Vest4		0.69
MutPred		0.18		Loss of sheet (P = 0.0357)
MVP		0.27
MPC		0.49
ClinPred		0.57	D
GERP RS		5.6
PromoterAI		0.0099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.28
Mutation Taster		=76/24	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: chr2-64778718;