2-64551746-A-T

Variant names:

• chr2-64551746-A-T
• rs149607255
• NM_203437.4:c.272A>T

Variant summary

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

The NM_203437.4(AFTPH):​c.272A>T​(p.Asp91Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D91N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AFTPH NM_203437.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47
• 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=0.2744897).

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.272A>T	p.Asp91Val	missense	Exon 2 of 10	NP_982261.2
	AFTPH	NM_001375969.1		c.272A>T	p.Asp91Val	missense	Exon 2 of 10	NP_001362898.1	A0A8Q3SIA4
	AFTPH	NM_001375970.1		c.272A>T	p.Asp91Val	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.272A>T	p.Asp91Val	missense	Exon 2 of 10	ENSP00000387071.1	Q6ULP2-1
	AFTPH	ENST00000238856.8	TSL:1	c.272A>T	p.Asp91Val	missense	Exon 2 of 9	ENSP00000238856.4	Q6ULP2-6
	AFTPH	ENST00000498706.5	TSL:1	n.390A>T		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461502 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726986

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111682

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.5
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.028	D
Polyphen		0.74	P
Vest4		0.50
MutPred		0.33		Gain of sheet (P = 0.0101)
MVP		0.25
MPC		0.45
ClinPred		0.93	D
GERP RS		4.5
PromoterAI		-0.0052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.40
Mutation Taster		=79/21	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: rs149607255; hg19: chr2-64778880;